Pneumococcal disease – setting the scene in 2022

Respiratory infections place a substantial strain on public health, and the COVID-19 pandemic highlighted challenges in the capacity of healthcare to adjust to surges in demand in respiratory care. Pneumonia is one of the leading causes of respiratory disease, hospitalization and death. In the Pfizer integrated symposium at ECCMID 2022 “Building on a strong foundation to address a new era to help protect against pneumococcal disease”, the current landscape of invasive pneumococcal disease (IPD) serotypes, community acquired pneumonia (CAP), and data on the recently approved PCV20 vaccine were discussed.

Following the introduction of pneumococcal conjugate vaccines (PCVs) in Europe, the IPD burden from Streptococcus pneumoniae serotypes included in PCV7 and PCV13 has decreased not only in vaccinated children, but also in the wider population as a result of herd immunity. In contrast to purified polysaccharide vaccines (PPV), PCVs are capable of reducing nasopharyngeal colonization (Dagan, 2019), which in turn reduces transmission and serotype spread in the population. Figure 1 further explores similarities and differences between polysaccharide and conjugate vaccines. 
 

 

While only a small fraction of PCV7 serotype disease prevails, mainly due to antimicrobial resistant strains, the residual prevalence of PCV13 serotype disease is significant, especially for serotypes 3 and 19A (de Miguel et al., 2021; Hanquet et al., 2019; Ladhani et al., 2018; Silva-Costa et al., 2021; van der Linden et al., 2019). The substantial residual prevalence rates in countries across Europe suggest there may be a limit to herd protection achieved with pediatric vaccination. An additional challenge is the increase of serotypes not included in the PCV13, which further compromises benefits of herd protection. Figure 2 outlines the most common serotypes in the EU between 2014 and 2018; an increase can be seen especially in incidence of non-PCV13 serotype 8, and PCV13 serotype 3 (ECDC, 2020).

The burden of CAP is high across Europe (Torres et al., 2018), and pneumococci remain the main causative agents. However, the etiologic diagnosis of CAP continues to be poor, with the causative agent remaining unknown in more than half of cases (Shoar and Musher, 2020). Recently, (serotype specific) urine antigen testing has brought noticeable improvement. A Spanish study showed that between 2016 and 2018 the serotypes most commonly identified in CAP were 3 and 8 (Torres et al., 2021).
 

Expanded valency vaccines and adult vaccination could potentially help address the pneumococcal disease burden. PCV20, recently approved in Europe and the United States (US) for prevention of invasive disease and pneumonia caused by Streptococcus pneumoniae in adults, contains the components of PCV13 plus an additional 7 serotypes. In phase 3 clinical studies, PCV20 was immunogenic and well tolerated with a similar safety profile to PCV13 in adults across age, sex, and race subgroups and regardless of previous pneumococcal vaccination (Apexxnar SPC). 
 

ECCMID 2022 References:

Changing serotype epidemiology of pneumococcal disease in Europe. Mário Ramirez (Lisbon, Portugal). Presented at ECCMID 2022 on 23 April 2022.

What can we learn from the PCV experience to date? Charles Feldman (Johannesburg, South Africa). Presented at ECCMID 2022 on 23 April 2022.

Addressing a new era to help protect against pneumococcal disease in adults. Wendy Watson, Pfizer employee (Pennsylvania, USA). Presented at ECCMID 2022 on 23 April 2022.


Additional references:

Apexxnar Summary of Product Characteristics 
https://www.ema.europa.eu/en/documents/product-information/apexxnar-epar-product-information_no.pdf. Oppdatert 14.02.2022.

Prevenar 13 Summary of Product Characteristics
https://www.ema.europa.eu/en/documents/product-information/prevenar-13-epar-product-information_no.pdf. Oppdatert 25.11.2020

Dagan R. Relationship between immune response to pneumococcal conjugate vaccines in infants and indirect protection after vaccine implementation. Expert Rev Vaccines. 2019 Jun;18(6):641-661. doi: 10.1080/14760584.2019.1627207. 

de Miguel S, Domenech M, González-Camacho F, et al. Nationwide Trends of Invasive Pneumococcal Disease in Spain From 2009 Through 2019 in Children and Adults During the Pneumococcal Conjugate Vaccine Era. Clin Infect Dis. 2021 Dec 6;73(11):e3778-e3787. doi: 10.1093/cid/ciaa1483. 

European Centre for Disease Prevention and Control. Invasive pneumococcal disease. In: ECDC. Annual epidemiological report for 2018. Stockholm: ECDC; 2020.

Hanquet G, Krizova P, Valentiner-Branth P, et al. Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination. Thorax. 2019 May;74(5):473-482. doi: 10.1136/thoraxjnl-2018-211767. 

Kobayashi M, Farrar JL, Gierke R, et al. Use of 15-Valent Pneumococcal Conjugate Vaccine and 20-Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022 Jan 28;71(4):109-117. doi: 10.15585/mmwr.mm7104a1. 

Ladhani SN, Collins S, Djennad A, et al. Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000-17: a prospective national observational cohort study. Lancet Infect Dis. 2018 Apr;18(4):441-451. doi: 10.1016/S1473-3099(18)30052-5. 

Shoar S, Musher DM. Etiology of community-acquired pneumonia in adults: a systematic review. Pneumonia (Nathan). 2020 Oct 5;12:11. doi: 10.1186/s41479-020-00074-3. 

Silva-Costa C, Gomes-Silva J, Prados L, et al. Pediatric Invasive Pneumococcal Disease Three Years after PCV13 Introduction in the National Immunization Plan-The Continued Importance of Serotype 3. Microorganisms. 2021 Jul 1;9(7):1428. doi: 10.3390/microorganisms9071428. 

Torres A, Cillóniz C, Blasi F, et al. Burden of pneumococcal community-acquired pneumonia in adults across Europe: A literature review. Respir Med. 2018 Apr;137:6-13. doi: 10.1016/j.rmed.2018.02.007

Torres A, Menéndez R, España PP, et al. The Evolution and Distribution of Pneumococcal Serotypes in Adults Hospitalized With Community-Acquired Pneumonia in Spain Using a Serotype-Specific Urinary Antigen Detection Test: The CAPA Study, 2011-2018. Clin Infect Dis. 2021 Sep 15;73(6):1075-1085. doi: 10.1093/cid/ciab307. 

Ouldali N, Varon E, Levy C, et al. Invasive pneumococcal disease incidence in children and adults in France during the pneumococcal conjugate vaccine era: an interrupted time-series analysis of data from a 17-year national prospective surveillance study. Lancet Infect Dis. 2021 Jan;21(1):137-147. doi: 10.1016/S1473-3099(20)30165-1. 

van der Linden M, Imöhl M, Perniciaro S. Limited indirect effects of an infant pneumococcal vaccination program in an aging population. PLoS One. 2019 Aug 1;14(8):e0220453. doi: 10.1371/journal.pone.0220453. 

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