A summary of presentations from the weekly Summit partner webinars
December 1, 2022 – The latest Summit Summary
- Pneumococcal Vaccination Recommendations Update – Miwako Kobayashi (CDC)
- Flu Surveillance Update – Katie Tastad (CDC)
- Announcements
Pneumococcal Vaccination Recommendations Update – Miwako Kobayashi (CDC)
Miwako Kobayashi, MD, MPH, Respiratory Diseases Branch, Division of Bacterial Diseases, CDC, gave a presentation on the new pneumococcal vaccination recommendations.
Two pneumococcal vaccines were licensed for use in U.S. adults before 2021, the 13-Valent pneumococcal conjugate vaccine (PCV13) or Prevnar13, and the 23 valent pneumococcal polysaccharide vaccine (PPSV23) or Pneumocax23. PPSV23 has been available since 1983, and the PCV 13 has been available since 2011. PCV13 contains 13 serotypes and PPSV23 contains 23.
In 2021, 2 new pneumococcal conjugate vaccines were licensed for use among U.S. adults. Those are the 15 valent pneumococcal conjugate vaccine (PCV15) or Vaxneuvance, and the 20-valent conjugate vaccine (PCV20) or Prevnar 20. PCV15 contains the serotypes contained in PCV13 plus two additional serotypes and PCV20 contains the 15 serotypes in PCV15 plus an additional 5 serotypes.
In October of 2021, the ACIP recommended the use of pneumococcal conjugate vaccines (PCV15 and PCV20) for adults. The new recommendations were published in MMWR, which was updated in January of this year. When ACIP updated the recommendations last year, use of PCV20 alone or use of PCV15 in series with PCV23 was recommended for high-risk adults who had not previously received a pneumococcal conjugate vaccine or whose previous vaccination history is unknown. This includes adults aged 65 years and older, and adults less than 65 years of age with certain risk conditions. An adult who has not received any pneumococcal vaccine is not recommended to receive PPSV23 alone under the current recommendations. However, because PCV13 was previously recommended for certain adults, there are adults who have already started their recommended vaccine series with PCV13. These adults are recommended to complete the series with PPSV23 according to when the new MMWR was published earlier this year.
During the ACIP meeting in October 2022, the ACIP discussed whether PPSV23 should be recommended for use among adults who previously received PCV13. This shared recommendation on PCV13 was updated in 2019 when routine use of PCV13 for this group was discontinued and no adult groups were recommended to receive PCV13. The groups of adults who were previously recommended to receive PCV13 include:
- Adults with an immunocompromising condition, such as a cochlear implant or cerebral spinal fluid leak, were recommended to receive one dose of PCV13 followed by various doses of PPSV23 depending on their underlying conditions and age
- Adults age 65+ without these conditions were recommended to receive PPSV23 routinely and PCV13 based on shared clinical decision-making.
The second consideration was the immunologic advantage of a pneumococcal conjugate vaccine compared with the pneumococcal polysaccharide vaccine. PCV13, 15, and 20 are all conjugate vaccines, and the capsular polysaccharide antigens are conjugated to a carrier protein, so this allows conjugate vaccines to induce a T-cell dependent response which confers immunity to young infants who did not respond well to polysaccharide vaccines. A T-cell dependent response also results in memory B-cell production. As a result, conjugate vaccines are expected to have longer duration of protection than polysaccharide vaccines.
Effectiveness against invasive pneumococcal disease (IPD) is supported by clinical data for both conjugate and polysaccharide vaccines, although limited effectiveness of PPSV23 has been reported in adults with immunocompromising conditions. PCV13 efficacy against vaccine-type non-invasive pneumonia was supported by a clinical trial, whereas data on PPSV23 effectiveness against this outcome have been variable.
The third consideration is the time since the last pneumococcal vaccination, especially for adults age 65+ since CDC did not recommend an additional dose of vaccine for these adults since they received the recommended vaccine doses. According to data from the CMS published in June of 2022, the median time since last PCV13 vaccination among Medicare beneficiaries age 65+ with or without having gotten PPSV23, was 5.6 years, ranging from 0–8.5 years. Among adults who received PCV13 followed by PPSV23, the median time since last PPSV23 dose was 3.1 years, ranging from 0–8.4 years. So, there were concerns that even through adults age 65+ have gotten PCV13/PPSV23, some of these adults may have been many years out from pneumococcal vaccination.
At the October ACIP meeting the ACIP discussed whether these adults who started the previous recommendation with PCV13 should receive the PCV20 as an option to PPSV23 for added protection. Some of the evidence that was considered by the ACIP to inform their discussion includes:
The burden of pneumococcal disease in adults
Pneumonia is the most common form of pneumococcal disease in adults. Invasive pneumococcal disease (IPD) is defined as an illness with pneumococcus identified in a normally sterile place such as the blood or cerebral spinal fluid. In 2018–2019, the case fatality ratio from IPD among adults age 65+ was 14%. Younger adults have a lower incidence of pneumococcal disease, but the risk is higher among those with an immunocompromising condition.
Adults with immunocompromising conditions have approximately 9–18 times higher incidence of pneumococcal disease when compared with adults without underlying conditions. Pneumococcal serotypes contained in PCV20 but not in PCV13 caused 27% of IPD in adults in 2018–2019. PCV13-type IPD incidence among adults age 65+ decreased after PCV13 use in children but remained stable in 2014–2019. PCV13 was recommended for adults age 65+ in late 2014 and this trend continued through 2019. This is part of the reason why the recommendations of routine use of PCV13 for adults age 65+ was updated in 2019.
Reduction in incidence of hospitalized PCV13-type pneumococcal pneumonia was observed after routine PCV13 use among a cohort of adults age 65+ in a Louisville cohort study from 2014–2016, when routine PCV13 use was recommended for this age group. On the other hand, CDC’s surveillance for noninvasive pneumococcal pneumonia assessed the incidence of hospitalized pneumococcal pneumonia in adults found that it did not decrease after routine PCV13 use among adults age 65+.
Data on safety and effectiveness of PCV20 use among adults who previously received PCV13
CDC did a systematic review of literature to identify any published data on PCV20 efficacy, effectiveness, immunogenicity, or safety in adults who previously received PCV13. There was no PCV20 efficacy or effectiveness data against clinical outcomes. CDC identified two phase 3 clinical trials that assessed safety or immunogenicity of PCV20 use among adults 65+ without immunocompromising conditions who previously received pneumococcal vaccination. The two studies did not compare the immunogenicity of PCV20 and PPSV23 among previously vaccinated adults. But the studies showed that in general, compared with adults who previously received PPSV23 1–5 years prior, adults who received PCV13 at least six months prior had comparable or improved immune response to PCV20.
In one study that provided data on safety, the proportion of serious adverse events among adults who received PCV20 after PCV13, was comparable to the group that received PPSV23 after PCV13.
Summary of cost-effectiveness analysis
Adults age 65+ without immunocompromising conditions who received both PCV13 and PPSV23 had the largest population size, therefore the comparison focused on the assessment of that population. The CDC model compared a cohort of adults who received both PCV13 and PPSV23 five years later (age 71 or 81, depending on when they received PCV13 and PPSV23) to adults who did not receive an additional dose of PCV20. Comparing across the three models, the CDC 5-year model resulted in the lowest cost-effectiveness estimates and the Merck model resulted within the range of CDC estimates.
In 2019 there was a discussion on whether to continue routine PCV13 use in series with PPSV23 for adults age 65+. The cost per quality gained in the base case was $562K for the CDC model and for the Pfizer model was $199K. The use of PCV20 or PCV15 in series with PPSV23 on previously vaccinated adults, which was the discussion that happened last year, was cost-saving. The new intervention saved money and had better health outcomes in most scenarios when the policy option was discussed last year.
Additional Considerations that could impact future adult pneumococcal vaccine recommendations
Unlike PCV13, PCV15 and PCV20 were licensed for use in adults first. PCV15 was recommended for use among children in June of this year and PCV20 is expected to be approved for use in 2023. Adults have benefited from indirect vaccination effects from pediatric vaccination. At this point it’s unknown how the use of these vaccines in children might impact the disease burden in adults in the future.
Also note that there are new pneumococcal vaccines that are in advanced stages of development. One is GSK’s 24-valent pneumococcal vaccine and the other is Merck’s 21-valent pneumococcal conjugate vaccine. Adult phase 2 study results are published for both products.
Updated ACIP Recommendations
With these and other evidence in consideration, the updated pneumococcal vaccine recommendations that were voted on by the ACIP in October this year are:
- Immunocompromised (cochlear implant or cerebral spinal fluid leak) adults who received PCV13+PPSV23 but have not completed their series are recommended to complete their pneumococcal vaccine series by receiving either a dose of PCV20 at lease 5 years after the last pneumococcal vaccines dose or PPSV23 as previously recommended
- Shared clinical decision-making is recommended regarding administration of PCV20 for adults age 65+ who completed their vaccine series with both PCV13 and PPSV23. If a decision to administer PCV20 is made, a dose of PCV20 is recommended at least five years after the last pneumococcal dose. Now there is an option based on shared clinical decision-making to receive a dose of PCV20.
- Adults who started the series with PCV13 but have not received PPSV23 are recommended to receive a dose of PCV20 at least one year after the PCV13 dose or PPSV23 as previously recommended to complete their pneumococcal vaccine series. Now there is an option for these adults to receive a dose of PCV20 and complete their recommended vaccine series.
The proposed timeline for publication of the updated recommendations are as follows:
- New pneumococcal vaccine recommendations will be reflected in the new Adult Immunization Schedule in early 2023
- New recommendations, along with the updated recommendations related to implementation will be published in MMWR later in 2023.
Questions
Q: For immunocompromised adults who received PCV13 but not PPSV23, please confirm that they can receive PPSV23 if >8 weeks but need to wait 1 year for PCV20.
Miwako Kobayashi: Yes, that is the policy option that was voted on.
Q: Any thoughts on what the pediatric recommendation might be once PCV20 gets approved for that age group?
Miwako Kobayashi: The ACIP Pneumococcal Vaccines Work Group are currently having discussions on that. We hope to be able to present that in future ACIP meetings.
Provider Organization Panel Discussion on Influenza Vaccination Promotion Activities and Challenges – Summit Partners
Katie Tastad, MPH, Influenza Division – Domestic Surveillance Team, CDC, gave a flu surveillance update for week 46. See: Weekly U.S. Influenza Surveillance Report | CDC.
Data from the end of May through November 19, 2022, shows an increase in influenza positive specimens and a steep increase in the percent positivity for flu over the past several weeks. Of the positive specimens, 99% of them have been influenza A and of those that were subtyped, 78% have been H3 and 22% H1. Only 1% have been influenza B and of those, all have been Victoria lineage. Most of the viruses have been antigenically similar to the vaccine reference strains.
Outpatient respiratory influenza-like illness (ILI), which is defined as fever, cough, and sore throat has seen a sharp increase in the last few weeks. During week 46, 6% of visits to a healthcare provider were for respiratory illness, which is above the national baseline of 2.5%. This increase occurred earlier than in prior seasons.
The highest ILI percentage is among those ages 0–4, followed by adults age 65+. ILI among 0–4 year–olds decreased in week 46 compared to week 45 but has remained stable or increased in other age groups.
Geographically, 35 jurisdictions had high or very high ILI activity and 8 had moderate activity. The areas with the highest ILI activity also matched with the areas that were recording the highest lab-confirmed flu. But other respiratory viruses are contributing to this as well.
There are also increases in long-term care (LTC) facilities and hospitalizations. The cumulative rate is already higher than is typically seen at this time of year and the highest rates are in those age 65+.
Death from pneumonia, influenza, and COVID-19 (PIC) are above the epidemic threshold for the entire COVID-19 pandemic. As far as flu is concerned, mortality is increasing. There have been 12 pediatric deaths so far this season due to influenza A viruses.
There have been at least 6.2 million symptomatic illnesses due to flu, three million medical visits, 53 thousand hospitalizations, and at least 2,900 deaths.
In summary, the flu activity is increasing earlier than is typically seen at this time of the year. It’s still too early to know whether this flu season is an early season or if it’s going to be a more severe season. It’s always important to remember that in the context of respiratory viruses, RSV, , CoVID-19, flu, and rhinoviruses are all elevated at the same time. It’s still a great time to get vaccinated for people who have not done so already.
Questions
Q: We still do not know whether we are heading into a severe flu season because of this concern that at the end of the season the cumulative hospitalization rates or mortality rates may not be any worse than a previous flu season. Is that correct?
Katie Tastad: I would say so. It’s hard to know whether this flu season just shifted earlier or if it will be more severe overall. You’re right that we don’t know what it’s going to look like in a cumulative way.
Q: Do you have any recommendations for Summit partners who are trying to message this to their policymakers?
Katie Tastad: I would say that we are still seeing increases and have not started to see any decrease in influenza or ILI. The holidays are coming up and there are plenty of very valid reasons why people should still be getting vaccinated. In addition to that, last season we had two peaks, so we don’t know what’s to come.
Q: Is there any information on vaccination match to circulating viruses?
Katie Tastad: So far there has been a good match antigenically and genetically. There isn’t a lot of data yet so far this season but what we have been seeing so far indicates that it’s been a good match.
Q: Is there a website or other resource with information on locations or organizations offering free or low-cost flu and other adult recommended vaccines, particularly Tdap, for persons without health insurance in the US?
Kelly L. Moore (Immuunize.org): A lot of those services are local. Contacting the local health department is probably the best thing that people can do to find out what is locally available.
Resource: CDC’s How to Pay for Vaccines
Q: Any recommendations on how to approach long term care facilities about immunization rates?
Katie Tastad: The one thing that might be helpful is that we have good data available to show them that can be used in messenging.
L.J Tan (Immunize.org): Another opportunity is to remind LTC facilities of the cost of an outbreak. Having to ameliorate an outbreak can run into the tens of thousands of dollars for a LTC facility, counting antivirals and so on. The fiscal approach tends to galvanize action. The other way is to educate healthcare providers. We know LTC staff are not highly vaccinated and when staff are not highly vaccinated, it makes it hard to get patients vaccinated.
Elizabeth Sobczyk (AMDA): We are working on a CDC cooperative agreement to improve rates among both staff and residents in the LTC setting––both skilled nursing facilities and assisting living. We are looking at moving into home and community-based services next year. So we’ve been working over the last year to put together a pilot to test evidence-based interventions in LTC and tell the story of what works and why. We are seeing great improvements in resident rates with reconciliation of process things like the use of standing orders. We are putting into place a yearly assessment. We are finding more challenges on the staff side, which is to be anticipated. We are working towards developing peer champions and building trust between administration and frontline staff. So, it’s not just “we care about you because we want you to get a flu shot,” it’s a year-round genuine effort to build that trust and to invest in the staff’s health. It’s a challenge for sure. But I think over time we will see some improvements as these peer champion programs and building trust efforts continue to build. I am happy to talk to anyone about what we have learned and what we have seen. We have resources at movingneedles.org for interventions to try and materials to back that up. I’m also happy to talk about what we are doing with the pilot. My email is esobczyk@paltc.org if anyone would like to connect.
Announcements
- We are trying to settle on dates for the Summit in person meeting in May in Atlanta. We have decided to settle on the dates for the meeting on May 9–11 and not May 16–18, which were the original dates.
- The Summit released Get Adults’ Vaccinations Back on Track, a 2-page clinician tip sheet on new CDC recommendations and tools to help adults catch up on needed vaccinations. NAIIS is a large coalition of public and private organizations dedicated to increasing immunization rates, co-led by Immunize.org, CDC, and the Health and Human Services Office of Infectious Disease and HIV/AIDS Policy.
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