The epidemiologic and biologic basis for classifying older age as a high-risk, immunocompromising condition for pneumococcal vaccine policy

Figures & data

Table 1. Medical conditions identified for pneumococcal vaccine recommendations by select countries

		US	UK	Germany	Australia	Canada	France	Italy	Japan	Spain
At-risk conditions
	Prior IPD									x
	Chronic neurologic conditions			x		x
	Chronic neurologic conditions with impaired management of oral secretions									x
	Chronic heart disease	x	x	x	x	x	x	x	x
	Chronic cardiovascular disease									x
	Chronic kidney disease		x			x	x		x	x
	Chronic liver disease	x	x		x	x	x	x		x
	Cirrhosis							x		x
	Chronic lung disease	x	x	x	x	x	x	x	x	x
	Severe asthma						x
	Diabetes mellitus	x	x	x	x	x	x	x		x
	Smoking	x			x
	Alcoholism	x			x			x		x
	Down syndrome				x					x
	Osteo-meningeal breccia						x
	Occupational risk (exposure to metal fumes)		x
	Celiac disease									x
High-risk conditions
	Cerebrospinal fluid leak	x	x	x	x	x		x	x	x
	Cochlear implant	x	x	x	x	x	x	x	x	x
	Intracranial shunts				x
	Sickle cell disease/other hemoglobinopathy	x	x	x	x	x	x	x
	Congenital or acquired asplenia or splenic dysfunction	x	x	x	x	x	x	x	x	x
	Congenital or acquired immunodeficiencies	x	x	x	x	x	x	x		x
	Immunocompromising therapies	x	x	x	x	x	x	x		x
	HIV infection	x	x	x	x	x	x	x	x	x
	HSCT recipient		x	x	x	x	x	x		x
	Malignant neoplasms including leukemia and lymphoma (e.g. Hodgkin’s disease)	x			x	x	x	x		x
	Disseminated neoplasms							x
	Nephrotic syndrome	x			x	x	x	x		x
	Solid organ or islet transplant	x		x	x	x	x	x		x
	Chronic renal/adrenal failure	x		x	x			x		x
	Phagocytic disorders (excluding chronic granulomatous disease)	x								x
	Multiple myeloma	x	x				x	x		x
	Complement disorder, systemic steroids treatment		x				x			x
	Chronic inflammatory diseases									x
	Deficiency or dysfunction of myeloid cells; properdin deficiencies; neoplastic diseases; autoimmune diseases			x			x

Key: US = United States, UK = United Kingdom, IPD = Invasive pneumococcal disease, HIV = human immunodeficiency virus, HSCT = hematopoietic stem cell transplant.

Table 2. Changes in the adaptive immune system in HIV infection and in older age

Change in adaptive immune response	Older age	HIV
CD4+ lymphopenia	-	+
Inverted CD4: CD8 ratio	+	+
Decreased thymic output	+	+
Reduced naïve cell numbers	+	+
Accumulation of late-differentiated CD8+ and CD4+ cells	+	+
Increased susceptibility to pneumococcal infection	+	+
Increased susceptibility to opportunistic infections	-	+

Key: ‘+’ = Change in adaptive immune response present, “-“ = Change in adaptive immune response absent; HIV = human immunodeficiency virus, CD4+ cells = Cluster of differentiation 4 cells or helper T cells, CD8+ = Cluster of differentiation 8 cells or killer T cells.

Figure 1. a-c: Comparison of disease incidence in healthy older adults vs high-risk younger adults

a. Comparison of invasive pneumococcal disease incidence in healthy older adults vs high-risk younger adults References: Ahmed et al. [28]; Shea et al. [29]; Pelton et al. [30]; van Hoek et al. [32]. b. Comparison of pneumococcal pneumonia incidence in healthy older adults vs high-risk younger adults References: Shea et al. [29]; Pelton et al. [30]. c. Comparison of all-cause pneumonia incidence in healthy older adults vs high-risk younger adults References: Shea et al. [29]; Pelton et al. [30]; Pelton et al. [31].

Figure 2. a-c: Comparison of disease incidence in at-risk older adults vs high-risk younger adults

a. Comparison of invasive pneumococcal disease incidence in at-risk older adults vs high-risk younger adults References: Ahmed et al. [28]; Shea et al. [29]; Pelton et al. [30]; van Hoek et al. [32]. b. Comparison of pneumococcal pneumonia incidence in at-risk older adults vs high-risk younger adults References: Shea et al. [29]; Pelton et al. [30]. c. Comparison of all-cause pneumonia incidence in at-risk older adults vs high-risk younger adults References: Shea et al. [29]; Pelton et al. [30]; Pelton et al. [31].

Table 3. Characteristics of studies reporting disease incidence by risk group for adults

Country	Time period	Study design, data source, and study specific considerations	Endpoints reported	Age groups reported (in years)	Reference
UK	2008/2009	Retrospective review of hospitalized IPD cases identified by national surveillance linked to clinical hospital statistics database. Data was not available to calculate the percent of age group or percent of the age group with the disease end point. An overall high-risk category or at-risk category as defined in other studies was not available. The category of ‘one or more risk factors’ was used as the at-risk group that included those with the following medical conditions: asplenia/splenic dysfunction, chronic respiratory disease, chronic heart disease, chronic kidney disease, diabetes, immunosuppression, cochlear implants, and cerebrospinal fluid leaks.	IPD	16–64, ≥65	van Hoek [32]
US	2007–2010	Retrospective cohort study of subjects identified from three integrated healthcare claims databases: (1) Truven Health Analytics MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits Databases; (2) IMS LifeLink PharMetrics Health Plan Claims Database; and (3) Optum Research Database.	IPD, PP, all-cause pneumonia	18–49, ≥65	Shea [29]
US	2013–2014	Retrospective review of IPD cases identified by Center for Disease Control and Prevention Active Bacterial Core surveillance linked to demographic and clinical information in the medical charts. Immunocompromising conditions reported include hematologic malignancies (multiple myeloma, leukemia, and lymphoma) and solid organ cancer (excluding nonmelanoma skin cancers). Mutually exclusive risk groups were not available for calculating the number of cases and person-time.	IPD	19–64, ≥65	Ahmed [28]
US	2013–2015	Retrospective cohort study of subjects identified from two integrated healthcare claims databases: (1) Truven Health Analytics MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits Databases and (2) Optum Clinformatics Claims Database. Individual medical conditions were not reported.	IPD, PP, all-cause pneumonia	18–49, ≥65 (65–74 and ≥75)	Pelton [30]
Germany	2009–2012	Retrospective cohort study of subjects identified by medical and drug claims from the Health Risk Institute Research Database.	All-cause pneumonia	18–49, ≥65 (65–74, 75–84, and ≥85)	Pelton [31]

Key: UK = United Kingdom, US = United States, IPD = Invasive pneumococcal disease, PP = Pneumococcal Pneumonia.

Ahmed SS, Pondo T, Xing W, et al. Early Impact of 13-valent pneumococcal conjugate vaccine use on invasive pneumococcal disease among adults with and without underlying medical conditions-united states. Clin Infect Dis. 2020 Jun 10;70(12):2484–2492. PubMed PMID: 31402387.

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Shea KM, Edelsberg J, Weycker D, et al. Rates of pneumococcal disease in adults with chronic medical conditions. Open Forum Infect Dis. 2014 Mar;1(1):ofu024. PubMed PMID: 25734097; PubMed Central PMCID: PMC4324183.

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Pelton SI, Bornheimer R, Doroff R, et al. Decline in pneumococcal disease attenuated in older adults and those with comorbidities following universal childhood PCV13 Immunization. Clin Infect Dis. 2019 May 17;68(11):1831–1838. PubMed PMID: 30239637; PubMed Central PMCID: PMC6522679.

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Van Hoek AJ, Andrews N, Waight PA, et al. The effect of underlying clinical conditions on the risk of developing invasive pneumococcal disease in England. J Infect. 2012 Jul;65(1):17–24. PubMed PMID: 22394683.

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Pelton SI, Shea KM, Farkouh RA, et al. Rates of pneumonia among children and adults with chronic medical conditions in Germany. BMC Infect Dis. 2015 Oct 30;15(1):470. PubMed PMID: 26515134; PubMed Central PMCID: PMC4627378.

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