The status of pneumococcal diseases and pneumococcal vaccination in Singaporean adults

INTRODUCTION Pneumococcal disease, including pneumococcal pneumonia and invasive pneumococcal disease (IPD), is associated with substantial morbidity and mortality, particularly among older adults.[1,2] Vaccines are an effective way to reduce pneumococcal disease in both children and adults.[3,4] However, the burden of pneumococcal disease, and vaccine uptake and coverage among adults vary between countries.[2] A clear picture of the status in individual countries is needed to inform local healthcare strategies. The aims of this expert opinion commentary are to give an overview our current understanding of pneumococcal disease in Singaporean adults, to identify data gaps and describe clinical concerns relating to Singapore's immunisation policies against pneumococcal diseases in adults, and to consider measures to narrow these gaps and address concerns. The insights provided are based on discussion by a group of experts in infectious diseases from hospitals and general practice in Singapore. PNEUMOCOCCAL DISEASE BURDEN AND SEROTYPES IN SINGAPOREAN ADULTS The number of cases of IPD among residents of Singapore is low, with 130 notifications recorded in 2018.[4] However, pneumonia is the second highest cause of mortality in the country, accounting for 18.4% of all deaths in 2021,[5] although the proportion of cases due to Streptococcus pneumoniae is not known. The incidence rates of IPD for the period 2013–2018 according to age distribution are shown in Figure 1.[4,6-9] The incidence rate of IPD increases in adults aged above 50 years and is highest in those aged ≥65 years (11.1 per 100,000 resident population in 2018),[4] an age group known to be at high risk for pneumococcal disease.[10]Figure 1: Age distribution incidence rate for invasive pneumococcal disease in Singapore (2013–2018).[ 4 , 6-9 ] *Rates are based on estimated mid-year resident population. ^55+ years. 2017: Excluded one foreigner seeking medical treatment in Singapore. 2018: Excluded four tourists and foreigners seeking medical treatment in Singapore.A retrospective analysis of data from all hospitals in Singapore for 1995–2004 reported a mean annual hospitalisation rate for pneumococcal disease of 56.4 per 100,000 population for adults aged ≥65 years; the case fatality rate was 4.7% among those aged 65–74 years and 8.4% for those aged ≥75 years.[11] Retrospective data from the four main public hospitals in Singapore for 1997–2013 showed that the in-hospital mortality rate due to pneumococcal disease was significantly higher among adults compared to children (18.5% vs. 3.1%, P < 0.001).[12] More than half (59.6%) of the adults who died were aged ≥65 years (odds ratio for pneumococcal-related death 2.5; 95% confidence interval [CI] 1.4–4.6). A case-control study of adults hospitalised with pneumococcal disease in 2015–2017 reported in-hospital mortality rates of 26.1% for IPD and 11.4% for non-IPD cases, and found that the age ≥85 years was an independent risk factor for mortality (adjusted odds ratio vs. age <65 years 10.78, 95% CI 4.10–28.37).[13] The most recent Communicable Diseases Surveillance Report for Singapore indicated that in 2018, serotypes 3, 19A and 23A were the most common in adults (12.8%, 9.6% and 7.4%, respectively).[4] Looking at coverage by pneumococcal vaccines, a retrospective study for the period 1997–2013 found that 62% of pneumococcal isolates from adults were serotypes covered by the 13-valent pneumococcal conjugate vaccine (PCV13), but that 30% of serotypes were not covered by any licensed vaccine.[12] Surveillance data from a single hospital in Singapore for 2012–2017 found that 68.7% of serotypes from adults aged ≥50 years with pneumococcal infections were covered by PCV13, 80.6% by PCV23 and 19.4% were non-vaccine serotypes.[14] National surveillance data for 2013–2018 indicated that the majority of IPD cases in adult Singaporeans involved serotypes covered by PCV13, with coverage rates ranging from 66.7% in 2013 to 52.1% in 2018.[4,6-9] With respect to other vaccines, approximately 0%–2.9% of IPD cases were serotypes covered by PCV15 that were not covered by PCV13, 3.1%–6.9% were serotypes covered by PCV20 that were not covered by PCV15 and 0%–6.9% were serotypes covered by 23-valent pneumococcal polysacchride vaccine (PPSV23) that were not covered by PCV20. It should be noted that currently, PCV13, PCV20 and PPS23, but not PCV15, are licenced in Singapore. The PCV20 received approval for use in adults in Singapore on 30 November 2022, but is not yet widely used. Vaccine serotypes that were not covered by any vaccine were found in 24.3%–28.7% of adult IPD cases in 2014–2017, increasing to 41.5% in 2018. These data may be consistent with studies on children that found that serotype coverage changed after the introduction of vaccines. In Singapore, coverage by PCV7 decreased from 78.6% early after its introduction (2005–2007) to 64.4% in 2008–2010 [Figure 2].[15] Studies in other countries have shown that the introduction of vaccination in children using PCV7, PCV10 or PCV13 has led to changes in pneumococcal serotype distribution among adults with IPD or pneumococcal pneumonia (serotype replacement).[16,17] Vaccines with broader serotype coverage may be needed, although additional data in adults are needed first.Figure 2: Trends in invasive pneumococcal disease serotypes among Singaporean children following introduction of pneumococcal vaccination.[ 15 ] [Reproduced with copyright permission from the International Society for Infectious Diseases (published by Elsevier Ltd).] 2005 — PCV7 commercialised, but uptake mainly in the private sector.[ 15 ] 2009 October — PCV7 included in National Childhood Immunisation programme (NCIP):[ 15 ] (a) aged < 1 year: 2 + 1 dosing (months 3, 5 and 12 [booster]); and (b) aged 1–5 years: one single dose. 2011 December — PCV13 introduced to NCIP.[ 16 ] PCV: pneumococcal conjugate vaccineCURRENT PNEUMOCOCCAL VACCINATION POLICIES FOR SINGAPOREAN ADULTS Pneumococcal conjugate vaccine was included in the Singapore National Childhood Immunisation Programme in 2009 (initially PCV7 and then PCV13 in 2011); it was administered as two primary doses at 3 and 5 months of age and as a booster dose at 12 months.[4,18] In 2018, 88.3% of children aged 2 years completed the primary course and 83.0% received the booster dose.[4] In 2013, the Expert Committee on Immunisation recommended one dose of PPSV23 for adults aged ≥65 years and for those aged 2–64 years who were at an increased risk of developing severe pneumococcal disease.[18] The National Adult Immunisation Schedule (NAIS)[4] and the Handbook on Adult Vaccination in Singapore 2020,[19] the latter of which is followed by most clinicians in Singapore, provide similar recommendations. Specifically, the handbook indicates that adults aged ≥65 years should receive one dose of PCV13 followed by one dose of PPSV23 one year later (8 weeks later in those with chronic renal failure). Adults aged 18–64 years with chronic diseases (pulmonary, cardiovascular or liver diseases, diabetes mellitus) should receive one dose of PPSV23; those with chronic renal failure, cochlear implants, cerebrospinal fluid leaks or at high risk of IPD (asplenia, immunocompromising states) should receive one dose of PCV13 followed by one dose of PPSV23 eight weeks later. A booster dose after 5 years is recommended for high-risk individuals.[19] In contrast to the paediatric population, the uptake of PCV among Singaporean adults is low. The Singapore National Population Health Survey 2020 found that the proportion of adults aged 65–74 years who reported ever receiving pneumococcal vaccination increased from 11.9% in 2017 to 14.4% in 2020.[20] Given the low coverage among adults, it is difficult to assess the impact of vaccination on pneumococcal disease within the population. EXPERT OPINION ON DATA GAPS We have identified several data/practice gaps that limit clinical evaluation of the adequacy of Singapore's vaccination policy against pneumococcal diseases in adult populations, and these are outlined in Box 1. The paucity of available scientific evidence related to pneumococcal vaccination, disease burden and serotype distribution was highlighted in a World Health Organization position paper, which also emphasised the need to fill these data gaps.[3] In relation to global vaccination coverage, the Centers for Disease Control and Prevention reported that the rate of coverage for the third dose of PCV in Southeast Asia was 58% in 2022 (up from 27% in 2020), but markedly lower than that of regions such as Europe (83%) and the Americas (78%).[21]Box 1: Expert opinion on data gaps in the adequacy of Singapore's vaccination policy against pneumococcal diseases in adult populations.RECOMMENDATIONS We propose that the following measures should be prioritised to improve understanding of pneumococcal diseases and the vaccination programme in Singapore's adult population. Access to serotype testing, including non-IPD cases, needs to be improved, with information sharing that is more real time. More robust surveillance is needed to monitor serotype distribution after implementation of NAIS, recommendations to evaluate if vaccine serotype coverage needs to be broadened. Vaccine coverage in the population at risk must increase, including improved vaccination uptake by older adults. To achieve the latter, it will be important to address patients' concerns about vaccination and to take into account factors such as vaccination fatigue associated with the coronavirus disease 2019 pandemic. Advocacy for pneumococcal vaccines should be undertaken by all healthcare providers. This could be further driven by the Healthier SG initiative with requirements for participating family physicians to meet a minimal proportion of eligible patients for pneumococcal vaccination. Better surveillance of prevalent serotypes in adults and children will inform the need for broader serotype coverage supported by higher-valent vaccines. Regional knowledge sharing about PCV serotyping data and vaccination data is imperative. In conclusion, improved reporting and analysis of local data are needed to understand the burden of pneumococcal disease among adults in Singapore and the impact of the vaccination programme in this population. Once all the data gaps have been identified and the relevant information has been gathered, this would set the stage for informed strategies to recommend the need for higher-valency pneumococcal vaccines in Singapore. With the rollout of the Healthier SG plan, focusing on preventative health, better uptake of the pneumococcal vaccine is anticipated, and such data should be made available to assist clinicians to further improve vaccine uptake. It is hoped that this article will help stimulate further discussion and action in this field. Acknowledgement We acknowledge that editorial assistance was provided by Ms Kathy Croom and Dr David P Figgitt, Content Ed Net, Singapore. Financial support and sponsorship Funding for editorial assistance was provided by Pfizer Singapore. Kurup A received an honorarium for participating in a meeting to discuss the issues raised in the paper. Leong HN received an honorarium for the meeting, and consultancy and speaking fees from Pfizer and Merck Sharp and Dohme. Leong CK received an honorarium for the meeting. Conflicts of interest There are no conflicts of interest.