Hong Kong Med J 2023 Feb;29(1):11-4 | Epub 8 Feb 2023
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
The role of a single-shot higher-valency pneumococcal vaccine in overcoming challenges regarding invasive pneumococcal disease in Hong Kong
Christopher KM Hui, MB, BS, FRCP1; Ivan FN Hung, MD, PDiPID2,3; Bing Lam, MB, BS, PDipID4; Ada WC Lin , MB, BS, PDipID5; Thomas MK So, MB, BS, FRCP6; Andrew TY Wong, MB, BS, MPH7; Martin CS Wong, MD, MPH8,9
1 813 Medical Centre, Hong Kong
2 Queen Mary Hospital, The University of Hong Kong, Hong Kong
3 Gleneagles Hospital Hong Kong, Hong Kong
4 Hong Kong Sanatorium & Hospital, Hong Kong
5 HKSH Medical Group, Hong Kong
6 Virtus Medical Centre, Hong Kong
7 Princess Margaret Hospital, Hong Kong
8 The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
9 Editor-in-Chief, Hong Kong Medical Journal
Corresponding author: Dr Christopher KM Hui (firstname.lastname@example.org)
Invasive pneumococcal disease (IPD), a major public health problem worldwide (including in Hong Kong),1 2 3 is a severe and potentially life-threatening infectious disease caused by the gram-positive bacterium, Streptococcus pneumoniae.1 2 The clinical manifestations of acute IPD vary among organ systems involved; they include severe and potentially fatal infections such as community-acquired pneumonia, meningitis, and sepsis.2 In Hong Kong, pneumonia has consistently been the second leading cause of death since 20124; it is associated with higher rates of hospitalisation and higher healthcare costs, particularly among older adults.5 6 Despite appropriate treatment, up to 50% of IPD survivors experience long-term complications, including respiratory, cardiovascular, and neurological sequelae.7 Invasive pneumococcal disease is associated with substantial healthcare and economic burdens; thus, it represents an acute public health problem in Hong Kong, particularly amid the coronavirus disease 2019 (COVID-19) pandemic. There is an urgent need to develop effective strategies that can mitigate the potential threat of an IPD outbreak.
Burden of invasive pneumococcal disease in Hong Kong
Invasive pneumococcal disease has been a statutorily notifiable disease in Hong Kong since January 2015.8 Between 2015 and 2019, the Centre for Health Protection recorded a median of 187 (range: 162-190) IPD cases per year; the emergence of COVID-19 in 2020 led to a dramatic decrease in the number of IPD cases in Hong Kong (Fig 1).3 However, the current IPD burden is severely underestimated because of underdiagnosis, and a high index of suspicion for IPD is a central aspect of differential diagnosis. Because the clinical symptoms of IPD overlap with the symptoms of other respiratory illnesses, inexperienced physicians may experience challenges regarding specimen collection (ie, samples may be inappropriately or inadequately collected); such challenges contribute to the underutilisation of diagnostic tests and underreporting of IPD.
Because S pneumoniae is transmitted by direct contact with respiratory secretions from patients with IPD and from healthy carriers,2 9 public health measures (eg, mask wearing, social distancing, travel restrictions, and quarantine) that were implemented to prevent the transmission of severe acute respiratory syndrome coronavirus 2 also reduced the spread of S pneumoniae; thus, the number of IPD cases has decreased since the beginning of 2020 (Fig 1).3 As Hong Kong emerges from the COVID-19 pandemic, the gradual relaxation of public health intervention measures is expected to result in an increased number of IPD cases. Moreover, seasonality could contribute to a sudden increase in IPD cases because respiratory diseases (eg, pneumococcal infection and influenza) are generally more prevalent during winter and early spring.10 11 Notably, Israel experienced a nationwide outbreak of S pneumoniae serotype 2 between 2015 and 2019, despite the availability of vaccination programmes.12 Such outbreaks highlight the need to formulate effective strategies for early disease prevention.
Figure 1. Number of invasive pneumococcal disease cases in Hong Kong, 2009-20223
Pneumococcal vaccination in Hong Kong
Two types of pneumococcal vaccines are available to prevent IPD: pneumococcal polysaccharide vaccines (PPSVs) and pneumococcal conjugate vaccines (PCVs). The 23-valent PPSV (PPSV23) contains purified capsular polysaccharide antigens from 23 distinct S pneumoniae serotypes, whereas PCVs—including PCV13, PCV15, and PCV20—contain purified capsular polysaccharide antigens from 13, 15 or 20 serotypes of S pneumoniae conjugated to a nontoxic variant of diphtheria toxin (CRM197), along with aluminium phosphate as an adjuvant.13 14 In contrast to PPSVs, the conjugated complexes contained in PCVs exert long-term protection because they are able to stimulate T-cell-dependent immune response to generate immune memory for the specific S pneumoniae serotypes covered by the vaccine.15 Importantly, clinical trials and real-world evidence have consistently demonstrated the effectiveness of PCV13 in providing serotype-specific protection against IPD.2 13 16 Although IPD can occur at any age, an increased risk of onset is associated with various factors; mortality is substantially higher in children <2 years and adults aged ≥65 years.10 13 In Hong Kong, the current recommendations for pneumococcal vaccination by the Centre for Health Protection prioritise adults aged ≥65 years with high-risk conditions,17 consistent with recommendations from the United States Advisory Committee on Immunization Practices.18 Specifically, pneumococcal vaccine-naïve individuals with high-risk conditions are recommended to receive one dose of PCV13, followed by one dose of PPSV23 at 1 year after PCV13 vaccination.17
Since 2017, the Hong Kong government has provided free or subsidised pneumococcal vaccination to eligible individuals through the Government Vaccination Programme (GVP) and the Vaccination Subsidy Scheme (VSS).19 Despite this governmental support, rates of vaccine uptake and participation in GVP and VSS remain low.19 Concerns regarding vaccine efficacy, poor understanding of the disease, and lack of clarity regarding vaccine schedules are some of the major challenges that limit pneumococcal vaccination among adults in Hong Kong.19 Another limiting factor is vaccine hesitancy related to perceived vaccination burden and fatigue.20
Current serotype burden in Hong Kong
Data from continuous surveillance of pneumococcal serotypes have facilitated analyses of serotypes isolated from the community, which have yielded insights regarding the effectiveness and limitations of pneumococcal vaccination programmes. Since the implementation of pneumococcal vaccination in Hong Kong, the incidence of IPD involving vaccine-covered serotypes has considerably decreased. However, because of low vaccination rates in recent years, PCV13-covered serotypes (including serotypes 3, 19F, and 19A) have been identified in half of all reported IPD cases (Fig 2).3 21 22 23 Importantly, although it is covered by PCV13 and PPSV23, serotype 3 remains a major cause of IPD because its unique polysaccharide capsule resists detection by vaccine-induced antibodies.24 Moreover, the emergence of non-vaccine serotypes (Fig 2; ie, serotype replacement) also poses a public health threat.23 25
Figure 2. Number of reported pneumococcal serotypes among IPD patients aged ≥18 years in Hong Kong, 2019-20223
A higher-valency vaccine for broader protection against invasive pneumococcal disease
Considering the current challenges in Hong Kong, a higher-valency PCV (eg, PCV20) could partly address the potential public health problem associated with serotypes that are not covered by the Hong Kong vaccination programme. The 20-valent PCV provides broader protection against IPD; a single dose contains seven new serotypes, in addition to the serotypes covered by PCV13.26 Phase 3 studies of clinical efficacy have demonstrated that PCV20 is noninferior to PCV13 and PPSV23 across a subset of age-groups, regardless of pneumococcal vaccination history and high-risk conditions.27 28 Importantly, PCV20 can be concurrently administered with influenza and COVID-19 vaccines.26
In October 2021, the Advisory Committee on Immunization Practices recommended one dose of PCV20 alone, or serial immunisation (PCV15, followed by PPSV23), for all PCV/PPSV-naïve adults aged ≥65 years and PCV/PPSV-naïve adults aged 19-64 years with high-risk conditions.26 The implementation of a PCV20 single-shot vaccination programme could be a cost-effective strategy to address the current burden of IPD cases that involve serotypes covered by PCV13 and serotypes unique to PCV20.29 Furthermore, the convenience of a simplified vaccination schedule could improve vaccine uptake.
Overcoming challenges in Hong Kong and implementing preventive strategies against invasive pneumococcal disease
The government and physicians play key roles in promoting pneumococcal vaccination and improving vaccine uptake, particularly among older adults. Because the perceived low burden of IPD may reduce the rate at which physicians recommend vaccination for their patients,30 there is a need to improve physician awareness regarding IPD and the benefits of pneumococcal vaccines for individuals with an increased risk of IPD.
Continuing medical education programmes for physicians could cover periodic updates regarding the IPD burden in Hong Kong, current pneumococcal vaccine schedules, proper sample collection methods, and appropriate diagnostic tests for confirmation of IPD in patients with relevant symptoms. These initiatives can improve early diagnosis and treatment of IPD, facilitate accurate data collection regarding IPD incidence, and help to manage the underestimated burden of IPD. Additionally, government-led public education campaigns that focus on bridging knowledge gaps with respect to (i) the public health impact of IPD (a vaccine-preventable disease), and (ii) vaccine accessibility through GVP and VSS, could help to overcome vaccine hesitancy and improve vaccine uptake in Hong Kong.
Conflicts of interest
All authors declare no conflict of interest.
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
Funding for this study was provided by Pfizer Hong Kong. Editorial and medical writing support was provided by Dr Analyn Lizaso from Weber Shandwick Hong Kong, funded by Pfizer Hong Kong.
1. Wahl B, O’Brien KL, Greenbaum A, et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15. Lancet Glob Health 2018;6:e744-e757. Crossref
2. Weiser JN, Ferreira DM, Paton JC. Streptococcus pneumoniae: transmission, colonization and invasion. Nat Rev Microbiol 2018;16:355-67. Crossref
3. Centre for Health Protection, Department of Health, Hong Kong SAR Government. Report on IPD. Available from: https://www.chp.gov.hk/en/resources/29/636.html. Accessed 6 Aug 2022.
4. Centre for Health Protection. Death rates by leading causes of death, 2001-2021. Available from: https://www.chp.gov.hk/en/statistics/data/10/27/117.html. Accessed 12 Nov 2022.
5. Li X, Blais JE, Wong IC, et al. Population-based estimates of the burden of pneumonia hospitalizations in Hong Kong, 2011-2015. Eur J Clin Microbiol Infect Dis 2019;38:553-61. Crossref
6. Man MY, Shum HP, Yu JS, Wu A, Yan WW. Burden of pneumococcal disease: 8-year retrospective analysis from a single centre in Hong Kong. Hong Kong Med J 2020;26:372-81. Crossref
7. Brooks LR, Mias GI. Streptococcus pneumoniae’s virulence and host immunity: aging, diagnostics, and prevention. Front Immunol 2018;9:1366. Crossref
8. Hong Kong e-Legislation. Cap. 599 Prevention and Control of Disease Ordinance. Available from: https://www.elegislation.gov.hk/hk/cap599" target="_blank. Accessed Sep 2022.
9. Chan KP, Ma TF, Ip MS, Ho PL. Invasive pneumococcal disease, pneumococcal pneumonia and all-cause pneumonia in Hong Kong during the COVID-19 pandemic compared with the preceding 5 years: a retrospective observational study. BMJ Open 2021;11:e055575. Crossref
10. Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. 14th edition. 2021. Available from: https://www.merle-arbeitsmedizin.de/wp-content/uploads/2022/02/CDC-Pink-Book-Version-14th-Edition.pdf. Accessed Nov 2022.
11. McCullers JA. Insights into the interaction between influenza virus and pneumococcus. Clin Microbiol ev 2006;19:571-82. Crossref
12. Dagan R, Ben-Shimol S, Benisty R, et al. A nationwide outbreak of invasive pneumococcal disease in Israel caused by Streptococcus pneumoniae serotype 2. Clin Infect Dis 2021;73:e3768-77. Crossref
13. Bridy-Pappas AE, Margolis MB, Center KJ, Isaacman DJ. Streptococcus pneumoniae: description of the pathogen, disease epidemiology, treatment, and prevention. Pharmacotherapy 2005;25:1193-212. Crossref
14. Centers for Disease Control and Prevention. About pneumococcal vaccines. Available from: https://www.cdc.gov/vaccines/vpd/pneumo/hcp/about-vaccine.html. Accessed 12 Nov 2022.
15. Berger A. Science commentary: why conjugate vaccines protect longer. BMJ 1998;316:1571. Crossref
16. Theilacker C, Fletcher MA, Jodar L, Gessner BD. PCV13 vaccination of adults against pneumococcal disease: what we have learned from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA). Microorganisms 2022;10:127. Crossref
17. Centre for Health Protection Scientific Committee on Vaccine Preventable Diseases. Updated recommendations on the use of pneumococcal vaccines for high-risk individuals. Available from: https://www.chp.gov.hk/files/pdf/updated_recommendations_on_the_use_of_pneumococcal_vaccines_for_high-risk_individuals.pdf. Accessed 6 Oct 2022.
18. Morga A, Kimura T, Feng Q, Rozario N, Schwartz J. Compliance to Advisory Committee on Immunization Practices recommendations for pneumococcal vaccination. Vaccine 2022;40:2274-81. Crossref
19. Huang J, Mak FY, Wong YY, et al. Enabling factors, barriers, and perceptions of pneumococcal vaccination strategy implementation: a qualitative study. Vaccines (Basel) 2022;10:1164. Crossref
20. Su Z, Cheshmehzangi A, McDonnell D, da Veiga CP, Xiang YT. Mind the “Vaccine Fatigue”. Front Immunol 2022;13:839433. Crossref
21. Ho PL, Law PY, Chiu SS. Increase in incidence of invasive pneumococcal disease caused by serotype 3 in children eight years after the introduction of the pneumococcal conjugate vaccine in Hong Kong. Hum Vaccin Immunother 2019;15:455-8. Crossref
22. Subramanian R, Liyanapathirana V, Barua N, et al. Persistence of pneumococcal serotype 3 in adult pneumococcal disease in Hong Kong. Vaccines (Basel) 2021;9:756. Crossref
23. Hon KL, Chan KH, Ko PL, et al. Change in pneumococcus serotypes but not mortality or morbidity in pre- and post-13-valent polysaccharide conjugate vaccine era: epidemiology in a pediatric intensive care unit over 10 years. J Trop Pediatr 2018;64:403-8. Crossref
24. Luck JN, Tettelin H, Orihuela CJ. Sugar-coated killer: serotype 3 pneumococcal disease. Front Cell Infect Microbiol 2020;10:613287. Crossref
25. Lo SW, Gladstone RA, van Tonder AJ, et al. Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international wholegenome sequencing study. Lancet Infect Dis 2019;19:759-69. Crossref
26. 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;71:109-17. Crossref
27. Essink B, Sabharwal C, Cannon K, et al. Pivotal phase 3 randomized clinical trial of the safety, tolerability, and immunogenicity of 20-valent pneumococcal conjugate vaccine in adults aged ≥18 years. Clin Infect Dis 2022;75:390-8. Crossref
28. Cannon K, Elder C, Young M, et al. A trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in populations of adults ≥65 years of age with different prior pneumococcal vaccination. Vaccine 2021;39:7494-502. Crossref
29. Mendes D, Averin A, Atwood M, et al. Cost-effectiveness of using a 20-valent pneumococcal conjugate vaccine to directly protect adults in England at elevated risk of pneumococcal disease. Expert Rev Pharmacoecon Outcomes Res 2022;22:1285-95. Crossref
30. Mui LW, Chan AY, Lee A, Lee J. Cross-sectional study on attitudes among general practitioners towards pneumococcal vaccination for middle-aged and elderly population in Hong Kong. PLoS One 2013;8:e78210. Crossref