March 1, 2018

March 1, 2018

Announcements – L.J Tan (IAC)

L.J reminded call participants to register for the upcoming NAIIS meeting and the National Immunization Conference. He also reminded callers about the looming deadline to provide comments on the two immunization related HEDIS measures which were described during the February 15, 2018 Summit Call.

ACIP Adult Immunization Summary – David Kim (CDC)

David provided information on adult immunization issues discussed at the February ACIP meeting. He noted that votes were taken on several topics (hepatitis A, Heplisav-B, and LAIV) which will be discussed by others during today’s call.

David reported that presentations were provided on HPV epidemiology, and the Committee discussed potential changes to the upper age limit for males receiving HPV vaccine in order to harmonize it with the female recommendation. The Committee also heard data on the effects of PCV13 on pneumococcal disease in persons age >65 years. Data is limited on the direct and indirect effects of this vaccine since it was recommended for adults. The Pneumococcal Vaccine Workgroup will continue to monitor available data and report back to ACIP at future meetings.

In 2015, the ACIP voted that MenB vaccine may be administered to young adults age 16–23 years. Enhanced surveillance in college age students indicated that, although the risk is extremely low, the incidence of meningococcal disease among college students age 18–21 years is greater than young adults in the same age group who do not attend college. The Workgroup suggested ACIP should consider providing additional clinical decision-making guidance for use during pre-college health visits.

The Evidence-Based Workgroup presented an Evidence to Recommendations (EtR) framework for ACIP in rendering any future recommendations. The ACIP approved this proposal. The six components included in the framework are: (1) problem, (2) benefits and harm, (3) values, (4) acceptability of the recommendation by providers and the public, (5) resource use, and (6) feasibility. Additional details on this EtR framework will be provided at future meetings.

ACIP Hepatitis B Update – Sarah Schillie (CDC)

ACIP voted to recommend Heplisav-B for persons age >18. The vaccine is a 2-dose series, with doses separated by at least 1 month. The vaccine uses a novel adjuvant (1018) that enhances the body’s response to hepatitis B surface antigen, resulting in increased antibody levels when compared to persons receiving one of the existing HepB vaccines. This enhanced protection is also seen among persons with traditionally poor HepB vaccine response, such as those who are older or who have diabetes or renal disease. Post-marketing studies will continue to be monitored for people such as those with autoimmune disease and experiencing cardiac events. Providers are encouraged that this vaccine will increase coverage rates and provide improved seroprotection in many persons.

Heplisav-B Vaccine – Randall Hyer (Dynavax)

Dr. Hyer provided an overview on Heplisav-B (Dynavax). He pointed out the impact of hepatitis B disease in the U.S. is significant, with an estimated 20,000 new infections each year. There was a 21% increase in cases from 2014 to 2015, the last years for which surveillance data is available. Approximately 95% of these new cases were in adults. An estimated 2.2 million persons in the U.S. are living with hepatitis B, which leads to cirrhosis and liver cancer and results in approximately 5,000 deaths annually.

ACIP has a risk-based approach to vaccination centered on sexual, parenteral, and occupational exposures. In 2011, ACIP adopted recommendations for persons with diabetes, who have a 2.1-fold increased risk of developing acute hepatitis B. These persons also have higher hospitalization rates (~53%) and a case fatality rate approximately 2.5 times higher than persons who do not have diabetes. They also are twice as likely to develop long-term complications compared with persons who do not have diabetes. This is a growing problem in the U.S., with almost 23 million adults diagnosed with diabetes and approximately 1.5 million new cases diagnosed annually. The mean age at diagnosis is age 54 years, which means they likely have not been immunized. (Childhood vaccine recommendations were adopted in the 1990s.) Although national groups (e.g., CDC and the National Academies of Science, Engineering, and Medicine) have adopted goals to eliminate viral hepatitis, we continue to see increasing numbers of cases.

Adherence to the current 3-dose hepatitis B vaccine schedule is challenging. A Vaccine Safety Datalink study indicated only 81% of persons received >2 of the recommended 3 doses, and just over one-half (54%) completed the 3-dose series in one year. Figures showed even poorer adherence in a San Diego STD clinic serving high risk men having sex with men (MSM). In this setting, only 64% of MSM received 2 doses in 5 years, and less than one-half (43%) completed the series within 5 years.

As noted in the Heplisav-B monograph and package insert, the vaccine is indicated for use against all known subtypes of hepatitis B virus in adults age >18 years. It is administered IM as 2 doses given at least 1 month apart. The vaccine is contraindicated in persons with a severe allergic reaction to a previous dose. The most common adverse reactions reported within 7 days of vaccination were injection site pain, fatigue, and headache.

Heplisav-B contains the same yeast-derived recombinant hepatitis B surface antigen that is used worldwide. The adjuvant in the vaccine is a Toll-like receptor 9 (TLR9) agonist 1018, which differs from the alum used in currently licensed vaccines. It is provided in 0.5 mL dose vials.

Dr. Hyer provided significant detail on three studies (HBV-10, HBV-16, and HBV-23) that compared Heplisav-B directly with Engerix-B. Of note, the study populations included a large number of persons who were African-American, as well as persons who were smokers. Results of these studies were published in Vaccine in 2012 (HBV-10), 2013 (HBV-16), and 2018 (HBV-23). In summary, the clinical studies indicated that, when compared to Engerix-B, Heplisav-B:

  • Induced high rates of seroprotection in all populations studied (including populations with reduced response to Engerix-B, such as persons with diabetes and people who were older, obese, or smokers);
  • Provided earlier seroprotection;
  • Had a similar safety profile;
  • Was administered in a 2-dose schedule over 1 month.

In response to a question, Dr. Hyer noted that Dynavax is working closely with CDC and other groups to provide effective communications about this vaccine. One of the major challenges presented is the apathy of many adult providers to the importance of hepatitis B immunization. In particular, there is tremendous unawareness about the importance of this vaccine in persons with diabetes. Dynavax is working with partners such as hepatitis B patient advocacy groups and medical associations to raise awareness about prevention of hepatitis B disease and the importance of immunization.

Following a question about the minimum interval for the vaccine, Sarah Schillie noted that the vaccine recommendations (currently scheduled for release in the April 20 MMWR) are expected to adhere to the standard ACIP grace period of 4 days for a minimum interval. Therefore, Heplisav-B doses given at an interval more than 4 days short of the recommended 1 month minimum interval will be considered invalid and will need to be repeated.

ACIP Hepatitis A Update – David Kim (CDC)

During the ACIP meeting, the GRADE analysis for the use of hepatitis A vaccine in people age >40 years was reviewed. Additional analyses were discussed for infants age <6 months, 6–11 months, and >12 months.

ACIP made the following recommendations related to hepatitis A vaccine:

  • The vaccine is recommended for post-exposure prophylaxis (PEP) for all persons age >12 months. Prior to this, IG was recommended for certain groups of people. However, IG can be difficult to obtain in a timely manner, and ACIP felt allowing vaccine use for all persons for PEP was preferable. In addition to the vaccine, IG can be administered to persons age >40 years, depending on the physician’s assessment of risk.
  • Hepatitis A vaccine should be administered to infants age 6–11 months prior to international travel. This basically piggybacks on the MMR recommendation for this same age group. These infants should receive the 2-dose series of hepatitis A and MMR vaccines at age >12 months, as recommended.

Influenza Surveillance and ACIP Influenza Update – Alicia Budd (CDC)

Alicia provided highlights of the influenza surveillance report from week 7, ending February 17, 2018. We are beginning to see some signs that activity may be declining on a national level. The percentage of respiratory specimens testing positive for influenza in clinical laboratories was 25.4%, which is slightly below the level that had been holding relatively stable for the prior 5 weeks.

The percentage of specimens testing positive for influenza A (58.2%) has continued to trend downward, while the percentage of influenza B specimens (41.8%) is on the rise. At least 7 of the 10 public health regions appear to be past their peak in terms of reported positives. Data from public health laboratories indicates 65% of tested viruses were influenza A and 35% were influenza B. Of the subtyped influenza A viruses, 73.7% were of the H3 variety, and 70.2% of the B viruses for which lineage information was available were B Yamagata. When compared with previous weeks, these percentages indicate that the amount of B viruses and H1 viruses are continuing to increase as the season progresses. Specimens characterized since May continue to be antigenically and genetically similar to the reference virus for this season’s vaccine. As of early February, the antigenic similarity is lower for egg-grown virus (64%) than cell-grown virus (98%). Of the several hundred viruses that have been tested, only 4 have shown any antiviral resistance. All of these virus samples were H1N1, which is not the predominant strain this season.

Nationwide, influenza-like illness (ILI) activity was at 6.4%, well above the baseline of 2.2% However, this was below the 7.4% reported in the previous week. All 10 HHS regions remain above their region-specific baselines, but this is beginning to decline. ILI information also is available on a state level, with activity summarized as high, moderate, low, or minimal. Last week, 39 states, New York City, the District of Columbia, and Puerto Rico reported high ILI activity, 5 states reported moderate ILI activity, 3 states reported low ILI activity, and 3 states reported minimal ILI activity.

Information from the Influenza Hospitalization Surveillance Network (FluSurv-NET) indicates an overall hospitalization rate of 74.5 per 100,000 population. The highest rate (323 per 100,000) was among adults aged >65 years, followed by adults aged 50–64 (80 per 100,000 population) and children aged 0–4 years 53 per 100,000 population). The adult rates are higher those seen in any previous seasons.

Based on reports from the National Center for Health Statistics (NCHS) surveillance system available for the week ending February 3, 9.5% of deaths were due to pneumonia and influenza (P&I). Although this is still above epidemic threshold levels, this is the second week in which we have seen a decline in the percentage of deaths attributed to P&I.

Thirteen (13) influenza-associated pediatric deaths were reported during week 7. For the 2017–2018 season, the total number of reported pediatric deaths is 97. Approximately one-third of these deaths were associated with influenza B viruses. Of the deaths associated with influenza A viruses, about ½ were associated with H1. Among the children who were vaccine-eligible and for whom vaccine status was known, approximately 20% had been vaccinated prior to illness onset.

In terms of geographic spread of influenza within a state (characterized as regional, local, sporadic, or no activity) as reported by state and territorial epidemiologists, 48 states and Puerto Rico reported widespread activity, 0 states reported regional activity, 2 states (Oregon and Hawaii), Guam, and the District of Columbia reported local activity, and 0 states and the U.S. Virgin Islands reported no influenza activity.

Alicia reported that the influenza session at the February ACIP meeting covered multiple topic areas, including a report on interim vaccine effectiveness data for the current season. MedImmune presented information on the potential causes of the lower VE for the H1 component of LAIV during prior seasons and reported on the company’s efforts to correct this problem. LAIV data throughout the world also was summarized. Following these presentations, the Committee voted to include LAIV in the list of vaccines available for use in the 2018–2019 season.

Finally, Alicia noted that WHO met last week to determine the vaccine formulation for the northern hemisphere during the upcoming season. After reviewing available data, WHO recommended that the H1 components remain the same as those used during the 2017–2018 season. The H3 virus will be updated to the strain WHO recommended for use in the southern hemisphere last September, i.e., A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus. WHO also recommended keeping a B Victoria virus lineage in the trivalent vaccine, although this will be updated to B/Colorado/06/2017-like virus. The B Yamagata virus strain used in the current season’s vaccine will remain unchanged. The FDA’s Vaccines and Related Biologic Products Committee (VRBPAC) is meeting today to adopt these recommendations.

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