March 7, 2019

Influenza Surveillance Update – Alicia Budd (CDC)
ACIP Meeting Summary – David Kim (CDC)
Other Items – L.J Tan (IAC)

Influenza Surveillance Update – Alicia Budd (CDC)

Alicia provided an update on influenza activity reported for week 8, ending February 23, 2019. Influenza activity continued to remain elevated.

For the week, 26.4% of specimens sent to clinical laboratories tested positive for influenza. This is similar to the percentage reported during the previous week. Influenza A (H1) remains the predominant strain reported, but the proportion of H3 reports is increasing. Looking at reports from the last three weeks, 4 regions (Regions 2, 4, 6, and 7) have been H3 predominant. Region 4 is the only region that has be H3 predominant for the entire season. The amount of reported influenza B circulating viruses continues to remain remarkably low.

During this season, more than 1,200 viruses have received antigenic and genetic characterization. All of the H1 viruses are the 6B1 clade (the same clade as the vaccine strain), though there is some genetic diversity within the clade. In spite of this diversity, 99% of H1 viruses tested are similar antigenically to the cell-propogated vaccine virus. Multiple clades and subclades of the H3 virus are co-circulating, with the 3C3a subclade continuing to increase. At 55%, this is now the predominant subclade in the U.S. this season. Sixty-three percent (63%) of the H3s are antigenically similar to the reference virus representing the vaccine strain. Most of the H3s that were low to the reference virus belong to clade 3C3a.

All of the Influenza B Yamagata viruses tested have belonged to the Y3 clade and are similar to the cell grown vaccine virus. For the Victoria viruses, co-circulation of several viruses is occurring, but the majority (65%) are similar to the V1A.1 reference virus. More than 1,200 viruses have been tested for resistance to oseltamivir, peramivir, and zanamivir. All viruses tested showed susceptibility to zanamivir, and more than 99% displayed susceptibility to oseltamivir and peramivir. Four H1 specimens have been found to have reduced susceptibility to oseltamivir and peramivir.

Outpatient visits for influenza-like illness (ILI) increased during the week to 5.0%. This is the highest ILI for this season. We have now been at or above the national baseline for 12 consecutive weeks. All 10 surveillance regions were above their region-specific baselines. However, Region 4 has declined for 2 weeks in a row. On a state level, 33 states experienced high ILI levels, 8 states reported moderate activity, and the remaining 9 states were at low or minimal activity levels.

Cumulative reports to FluSurv-NET this season indicate a rate of 32.1/100,000 lab-confirmed influenza hospitalizations. Highest hospitalization rates were seen in persons >65 years at almost 95.1/100,000, followed by the 0–4 age group at 45.5/100,000.

The percent of deaths reported due to pneumonia and influenza (P&I) has remained stable (7.1–7.2%) for several weeks.

Twenty-two (22) new influenza-associated pediatric deaths were reported to CDC during the last 2 weeks, bringing the total number of deaths reported this season to 56.

For the geographic spread of influenza during the week, 49 states reported widespread activity and 1 state (West Virginia) reported regional activity.

For the preliminary influenza burden reports released, an estimated 22.8–26.3 million persons have been ill with flu. Approximately half of those persons have received medical care, and 289,000–347,000 were hospitalized. An estimated 18.9–31.2 persons have died.

ACIP Meeting Summary – David Kim (CDC)

David provided a summary of the February 27–28 ACIP meeting. Discussions were held on multiple vaccines and votes were taken on 2 vaccines.

Japanese Encephalitis Vaccine
During this session, a routine review of existing recommendations (including considerations for newly available safety, immunogenicity, and risk data) was done, and votes on new indications and dosing schedules were taken. New data support strengthening current permissive booster dose recommendations—specifically, there’s 58%-83% seroprotection at 12–15 months after primary series.

Three separate votes were taken on JE vaccination recommendations, and each was approved unanimously (15–0). The votes:

strengthen permissive language to state that the vaccine is “recommended for residence, longer-term (>1 month) for exposure, and frequent travel”;
expand the recommended interval for the vaccine from 28 days to 7–28 days between doses for adults age 18–65 years; and
add that a booster dose should be given >1 year after the primary series for adults and children. (Previously there was no booster dose recommendation for children.)

The Japanese Encephalitis WG will be dissolved upon publication of these policy updates.

Anthrax Vaccine
During this session, ACIP voted to expand the interval between the primary series of anthrax vaccine adsorbed (AVA) and a booster dose to 3 years for persons not at high-risk but anticipating high-risk.

AVA is recommended for adults age 18–65 years exposed to anthrax spores, administered subcutaneously at 0, 2, and 4 weeks (combined with 42 days of antimicrobial prophylaxis).
During a public health emergency, AVA can be administered IM with dose-sparing options (2 full doses or 3 half doses).
ACIP also reviewed AVA in pre-exposure prophylaxis and discussed the use of the new AVA adjuvanted with CPG 7909 (AV7909, NuThrax) under emergency use authorization. AV7909, targeted for biologic license application in the fourth quarter of 2021, is administered IM at 0 and 2 weeks.
Based on limited data, AVA7909 appears safe and effective. AV7909 is expected to be added to the Strategic National Stockpile in July 2019 for PEP.

Influenza Vaccine
During this session, updates were provided on interim vaccine effectiveness (47% overall) and influenza epidemiology and surveillance. H1N1 predominated overall, but H3N2 predominated in the southeast and is increasing in other regions.

In addition, IIV and spontaneous abortion in the Vaccine Safety Datalink was presented. No significant association was found, and the findings support safety of influenza vaccination in pregnancy.

FDA-approved use of Afluria Quadrivalent for children aged 6 through 35 months was presented. This adds another influenza vaccine option for young children.

WHO’s Consultation on the Composition of Influenza Virus Vaccines selected strains for H1N1 and B strains for the 2019–20 season in February, but H3N2 strain selection will not take place until March 21 to allow for more data collection. That means the Vaccines and Related Biological Products Committee (VRBPAC) meeting scheduled for March 6 and subsequent FDA decision scheduled for March 21 will also be delayed. Implications for downstream effects of the delay are unknown.

HPV Vaccine
The ACIP heard presentations on the impact, cost-effectiveness, and economic modeling of “mid-adult” HPV vaccination. Current recommendations have a cost-effectiveness profile; mid-adult vaccination (<30years, <45years) would be much less cost-effective.

Policy options in 3 areas were discussed: 1) no change in routine vaccination; 2) harmonize upper ages for catch-up vaccination for females and males; and 3) if older than catch-up age, individual clinical decision through age 45 years. Discussion will continue during the June 2019 ACIP meeting.

Combination Hexavalent Vaccine
An overview of phase III clinical trials of the new pediatric hexavalent vaccine (DTaP, IPV, HepB, Hib) (Vaxelis, Merck) was presented by the manufacturer. The combination vaccine, designed to improve compliance, has been in use in the European Union since 2017. It was licensed by the FDA in December 2018, but the vaccine is not expected to be available until at least 2020. Evidence-to-recommendation framework will be presented at the June ACIP meeting, and a vote is expected.

Pneumococcal Vaccine
The ACIP was presented with a full evidence-to-recommendation framework and GRADE for the PCV13 recommendation for adults, including focused presentations on serotype 3.

PCV13-type disease burden has been dramatically reduced through indirect effects; the relatively small remaining fraction of disease is primarily caused by serotype 3. Also presented was information on PCV13’s direct effects on pneumonia as observed in national hospital discharge data and a comparison of economic analyses.

Take home messages on the use of PCV13 in immunocompetent adults ≥65 years in the context of the indirect effects observed to date were:

Pneumococcal disease is still of public health importance, but there remains uncertainty about pneumococcal pneumonia and mortality associated with PCV13-type disease;
Desirable effects from continued use of PCV13 in this population are expected to be small, but still outweigh risks; and
The use of PCV13 in series with PPSV23 in this population is probably not an efficient allocation of resources.

This discussion will continue during the June ACIP meeting, and a vote on the PCV13 recommendation for adults >65 years is expected at that time.

Meningococcal Vaccine
During this session, summaries of data on the persistence of immunity following the primary series of MenB-FHbp and MenB-4C and immunogenicity and safety of booster doses were presented by their respective manufacturers, followed by GRADE and evidence-to-recommendation framework for MenB booster doses.

Serogroup B antibody wanes 1–2 years after the primary series, and, after a booster dose, persists for at least 2 years. Based on limited data on booster doses, no serious adverse events were reported. Therefore, given the seriousness of meningococcal disease, a MenB booster dose is indicated after completion of primary series for those at increased risk.

Policy options for 2 groups at risk were discussed:

For persons with asplenia, complement deficiency, complement inhibitor use, or microbiologists, a MenB booster dose would be recommended 1 year following completion of a primary series, followed by booster doses every 2–3 years for as long as increased risk remains; and
for persons at increased risk during an outbreak, a one-time booster dose would be recommended if it has been ≥1 year since completion of a primary series.

These options will be discussed further and a vote is expected during the June ACIP meeting.

Zoster Vaccine
This session was for information sharing.

The recombinant zoster vaccine (RZV) shortage due to high demand will continue, and providers will continue to experience shipping delays. In 2018, 8.6 million doses were distributed. Post-licensure safety monitoring of RZV in VAERS is generally consistent with the safety profile in pre-licensure clinical trials. The Vaccine Safety Datalink detected a statistical signal based on a small number of Guillain-Barré syndrome (GBS) reports, but the data (100,000 doses given with 4 GBS cases) are insufficient to identify a safety issue. Safety monitoring will continue.

Hepatitis A vaccine
This session covered hepatitis A vaccine information and a discussion on HIV as a risk factor, as well as discussions of hepatitis A immunity after vaccination among persons living with HIV. GRADE analysis and evidence-to-recommendations framework of HepA usage in patients with HIV were presented. The result of the discussion was that HepA is safe and effective in persons with HIV infection. There was a discussion on the policy question “Should routine 2-dose HepA be given to adults with HIV?” This discussion will continue during the June ACIP meeting..

Other Items – L.J Tan (IAC)

- 2019 Summit In-Person Meeting Information Now Available Online – The 2019 Summit in-person meeting will be held in Atlanta, GA on May 14–16, 2019. Information on registration, submission of poster abstracts, and nominations for the 2019 Immunization Excellence Awards is available on the 2019 National Adult and Influenza Immunization Summit webpage. (Please note that the password to register for this invitation-only meeting is available by contacting L.J Tan.) If possible, please book your room either through the onscreen “pop-up” that appears after you register or later through the email you receive after completing your registration. This not only will give you access to the “preferred rate,” it also will help the Summit meet its lodging contractual agreement with the hotel.
- 2019 Immunization Excellence Awards and Poster Submissions – The deadline for nominations for the 2019 Immunization Excellence Awards closed on March 1. The Summit will continue accepting abstracts for poster presentations through March 15.