Role of pneumococcal vaccination in prevention of pneumococcal disease among adults in Singapore

Figures & data

Table 1 Singapore pneumococcal seroprevalence data

Study with key findings in PD	Predominant serotype (%)
	Children				Adults
	Associated with primary bacteremia	Associated with pneumonia	Associated with meningitis	No specified association	Associated with primary bacteremia	Associated with pneumonia	Associated with meningitis	No specified association
Ling and Tay 1990^Citation8,$	14	6B	6B		1	3	1
Overall mortality rate was 29.5%.	20	14	19A		11A	4	13
High incidence in males, extremes of ages, and Indian and Malay races		19A	19F		20	7F	34
						14
Chong et al 2008^Citation9	23F (30.8)	14 (33.9)	14 (30.8)
Diagnoses at presentation: pneumonia 63.3%; bacteremia 17%; meningitis 15.6%; other 4.1 %	14 (26.1)	6B (17.7)	19F (30.8)
	6B (I3)	23F (17.7)
	15 (7.7)	6A (8.1)
Hsu et al 2009^Citation27								14 (18.2)
Attributable mortality was 21.4%								3 (11.5)
								6B (8.3)
								8 (6.8)
								19F (6.3)
Vasoo et al 2010^Citation11				6B (16.9)
Dramatic increase in antibiotic resistance over the last 10–15 years in Singapore				23F (11.9)
				19F (10.2)
Singapore Ministry of Health 2012^Citation12,#				19A (39.7)				3* (12.9)
A decrease of 10.8% in invasive PD cases versus 2010				14 (15.5)				14 (11.1)
				6B (13.8)				8 and 19A (9.7)
								6B (9.2)
Singapore Ministry of Health 2013^Citation13,#				19A (51.6)				3* (14.9)
				6B (22.6)				7F (7.5)
PCV7 serotype coverage was modest (35.5%) versus PCV13 (65.9%) and PPV23 (79.3%)				3 (16.2)				19A (6.7)
								6B (6.7)

Notes:

$ Retrospective study from 1977–1986; serotype prevalence in percentage is not available.

# The latest data from the Singapore Ministry of Health. The report published in 2012 applies to the 2011 period and the 2013 report applies to the 2012 period.

* Associated with significantly high case-fatality rates in adults.

Abbreviations: PCV7, seven-valent pneumococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; PCV23, 23-valent pneumococcal conjugate vaccine; PD, pneumococcal disease.

Table 2 Effects of pneumonia on the cardiovascular system

Vascular endothelium and peripheral vessels	Decreased peripheral vascular resistance in most young adults, but increased peripheral vascular resistance in up to one-third of middle-aged adults (no data available for elderly patients); increased concentrations of endothelin-1 and adrenomedullin
Myocardium	Depression of left ventricular function; myocarditis; increased concentrations of troponins, BNP, and ANP
Cardiac rhythm	Acute cardiac arrhythmias
Coronary arteries	Possible acute inflammatory changes in atherosclerotic plaques; possible coronary vasoconstriction
Pulmonary circulation	Increased pulmonary artery pressures
Cardiac autonomic function	Impairment of cardiovascular autonomic reflexes
Coagulation	Increased procoagulant activity
Renal function and fluid and sodium balance	Increased production of vasopressin; decreased ACE activity; water retention; acute kidney injury

Note: Reprinted from The Lancet, vol 381, Corrales-Medina VF, Musher DM, Shachkina S, Chirinos JA, Acute pneumonia and the cardiovascular system, Pages 496–505,¹⁶ Copyright © 2013, with permission from Elsevier.

Abbreviations: ACE, angiotensin-converting enzyme; ANP, atrial natriuretic peptide; BNP, B-type natriuretic peptide.

Table 3 Serotypes included in pneumococcal vaccines

Vaccine	Serotypes included
PPSV23	1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F
PCV7	4, 6B, 9V, 14, 18C, 19F, and 23F
PCV10	1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F
PCV13	1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F

Abbreviations: PCV7, seven-valent pneumococcal conjugate vaccine; PCV10, ten-valent pneumococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Figure 1 Functional immune responses for pneumococcal serotype 1 (GMT) in the pivotal noninferiority trial (Study 004) measured pre- and post-vaccination using a functional OPA assay.

Notes: Antibodies were determined before first vaccination (pre-dose 1), 1 month after vaccination (1 month post), and 12 months after first vaccination (12 months post); and before the second vaccination 3–4 years later (pre-dose 2) and 1 month after the second vaccination (post-dose 2). An OPA titer that correlates with protection has not been defined. The dark straight line at GMT ∼140 represents the minimum GMT peaks attained following first dose of PCV13 to help understand amplification of response following revaccination. This demonstrates that PCV13 primed the immune system for a booster response to subsequent vaccination with either vaccine. In contrast, the PPSV23 vaccine inhibited the response to a second dose of the same vaccine, and this was seen for all of the serotypes (serotype 1 is shown in figure as an example). Reproduced from Paradiso PR. Pneumococcal conjugate vaccine for adults: a new paradigm. Clin Infect Dis. 2012;55(2):259–264, by permission of Oxford University Press.⁴³
Abbreviations: GMT, geometric mean titer; OPA, opsonophagocytic activity; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Figure 2 Functional immune responses for pneumococcal serotype 1 (GMT) in the pivotal noninferiority trial (Study 3005) measured pre- and post-vaccination using a functional OPA assay.

Notes: Study 3005⁶⁵ enrolled PPSV23 exposed individuals (mean age 77 years) to receive either PCV13 or PPSV23 again. Subjects were reimmunized 1 year later with PCV13 regardless of whether they had received PCV13 or PPSV23 the previous year. Antibodies were determined before first vaccination (pre-dose 1), 1 month after vaccination (post-dose 1), before the second vaccination (pre-dose 2), and 1 month after the second vaccination (post-dose 2). Study 3005 showed that PPSV23 also blunted the response to a dose of the conjugate vaccine (serotype 1 is shown in figure as an example). Reproduced from Paradiso PR. Pneumococcal conjugate vaccine for adults: a new paradigm. Clin Infect Dis. 2012;55(2):259–264, by permission of Oxford University Press.⁴³
Abbreviations: GMT, geometric mean titer; OPA, opsonophagocytic activity; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Table 4 Advisory Committee on Immunization Practices 2013 updates/highlights related to pneumococcal vaccination in adults

Updates for PCV13

– Adults ≥19 years* with immunocompromising conditions who have not previously received PPSV23 or PCV13 should receive a single dose of PCV13 followed by a dose of PPSV23 ≥8 weeks later.

– Adults ≥19 years with immunocompromising conditions who have previously received one or more doses of PPSV23, should receive a single dose of PCV13 ≥1 year after the last dose of PPSV23 was received.

– Recommendations for the second dose of PPSV23 remain unchanged (≥5 years after the first dose in adults aged 19–64 years with immunocompromising conditions and a single dose after age 65 years for all who received first dose before age 65 or later if ≥5 years have passed since the previous dose).

– When cancer chemotherapy or other immunosuppressive therapy is being considered, the interval between PPSV23 vaccination and initiation of immunosuppressive therapy should be ≥2 weeks. Vaccination during chemotherapy or radiation therapy should be avoided.

– No direct guidance on the timing of PCV13 in relation to chemotherapy or radiation therapy. But in general, PCV13 should be given first and ≥8 weeks before PPSV23 when both PCV13 and PPSV23 are indicated in adults.

– PCV13 has not yet been recommended for routine vaccination of older adults, but recommends PPSV23 for all adults aged ≥65 years.

Updates for PPSV23 (on revaccination)

– One-time revaccination 5 years after the first dose is recommended for persons aged 19–64 years with chronic renal failure or nephritic syndrome; functional or anatomic asplenia (eg, sickle cell disease or splenectomy); and for persons with immunocompromising conditions.

– Persons who received one or two doses of PPSV23 before age 65 years for any indication should receive another dose of the vaccine at age 65 years or later if ≥5 years have passed since their previous dose.

– No further doses are needed for persons vaccinated with PPSV23 at or after age 65 years.

Notes:

* PCV13 is licensed by the US Food and Drug Administration and Singapore Health Sciences Authority for use in adults ≥50 years of age only. Data from the Morbidity and Mortality weekly Report, Centers for Disease Control and Prevention.⁸³

Abbreviations: PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Table 5 Advisory Committee on Immunization Practices 2012 recommendations on medical conditions or other indications for administration PCV13 and PPSV23 for adults aged ≥19 years,* by risk group

Risk group	Underlying medical condition	PCV13	PPSV23
		Recommended	Recommended	Revaccination 5 years after first dose
Immunocompetent persons	Chronic heart disease†		✓
	Chronic lung disease§		✓
	Diabetes mellitus		✓
	Cerebrospinal fluid leak	✓	✓
	Cochlear implant	✓	✓
	Alcoholism		✓
	Chronic liver disease, cirrhosis		✓
	Cigarette smoking		✓
Persons with functional or anatomic asplenia	Sickle cell disease/other hemoglobinopathy	✓	✓	✓
	Congenital or acquired asplenia	✓	✓	✓
Immunocompromised persons	Congenital or acquired immunodeficiency¶	✓	✓	✓
	Human immunodeficiency virus infection	✓	✓	✓
	Chronic renal failure	✓	✓	✓
	Nephrotic syndrome	✓	✓	✓
	Leukemia	✓	✓	✓
	Lymphoma	✓	✓	✓
	Hodgkin’s disease	✓	✓	✓
	Generalized malignancy	✓	✓	✓
	Iatrogenic immunosuppression**	✓	✓	✓
	Solid organ transplant	✓	✓	✓
	Multiple myeloma	✓	✓	✓

Notes:

* All adults aged ≥65 years should receive a dose of PPSV23 regardless of previous history of vaccination with pneumococcal vaccine.

† Including congestive heart failure and cardiomyopathy, excluding hypertension.

§ Including chronic obstructive pulmonary disease, emphysema, and asthma.

¶ Including B- (humoral) or T-lymphocyte deficiency, complement deficiencies (particularly C1, C2, C3, and C4 deficiencies), and phagocytic disorders (excluding chronic granulomatous disease).

** Diseases requiring treatment with immunosuppressive drugs, including long-term systemic corticosteroids and radiation therapy. Reprinted from Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012;61(40):816–819.⁷⁴

Abbreviations: PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

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