Streptococcus pneumoniae serotype 19A: worldwide epidemiology

Figures & data

Table 1. Randomized controlled trials assessing the immunogenicity of PCVs against serotype 19A.

	PCV7				PCV10
	IgG GMC, μg/mL (95% CI)		OPA GMT (95% CI)		IgG GMC, μg/mL (95% CI)		OPA GMT (95% CI)
Study	Post-primary	Post-final	Post-primary	Post-final	Post-primary	Post-final	Post-primary	Post-final
Vesikari et al. [67]^a,b	0.11 (0.09, 0.13)	0.47 (0.37, 0.62)	4.5 (3.9, 5.3)	11.1 (7.3, 17.0)	0.08 (0.07, 0.09)	0.85 (0.73, 1.00)	8.6 (7.1, 10.5)	29.2 (22.3, 38.3)
Kim et al. [68]^a,c	0.12 (0.10, 0.14)	0.32 (0.24, 0.43)	5.3 (4.2, 6.7)	15.5 (8.1, 29.9)	0.29 (0.25, 0.33)	1.54 (1.27, 1.87)	10.9 (8.4, 14.3)	64.9 (44.6, 94.5)
Bermal et al. [69,70]^a,d	0.18 (0.15, 0.22)	0.58 (0.37, 0.91)	4.2 (3.8, 4.7)	8.7 (5.4, 14.2)	0.36 (0.31, 0.41)	3.22 (2.46, 4.21)	10.6 (7.9, 14.2)	89.3 (58.9, 135.4)
Bermal et al. [69,70]^a,e	0.12 (0.10, 0.15)	0.38 (0.25, 0.58)	4.0 (4.0, 4.0)	20.3 (8.8, 46.8)	0.29 (0.25, 0.34)	1.75 (1.27, 2.43)	10.1 (7.8, 13.1)	70.7 (45.3, 110.4)
105539 [71]^a,f	NS	NS	NS	NS	0.19 (0.16, 0.24)	0.87 (0.69, 1.11)	15.8 (11.2, 22.3)	27.2 (18.0, 41.2)
Wysocki et al. [72]^a,g	0.12 (0.1, 0.14)	0.35 (0.29, 0.42)	4.1 (3.9, 4.2)	8.7 (6.6, 11.4)	0.27 (0.22, 0.32)	1.19 (0.96, 1.47)	11.2 (8.1, 15.4)	48 (32.1, 71.9)
					0.22 (0.19, 0.27)	1.12 (0.89, 1.42)	8.4 (6.4, 11.0)	46.6 (30.8, 70.4)
					0.18 (0.15, 0.22)	0.75 (0.6, 0.94)	7.1 (5.6, 9.0)	18.9 (13.0, 27.4)
van den Bergh et al. [73]^a,h	0.08 (0.07, 0.10)	NS	4.9 (4.4, 5.4)	NS	0.10 (0.09, 0.13)	NS	9.0 (6.9, 11.7)	NS
					0.09 (0.08, 0.11)	NS	8.0 (6.3, 10.2)	NS
	PCV7				PCV13
Kieninger et al. [76]^i	0.64 (0.58, 0.71)	3.79 (3.40, 4.21)	7 (5, 9)	59 (37, 94)	3.26 (2.97, 3.59)	9.58 (8.68, 10.58)	442 (361, 543)	1349 (1089, 1672)
Yeh et al. [77]^j	0.89 (0.79, 0.99)	3.54 (3.15, 3.98)	7 (5, 8)	268 (164, 436)	2.07 (1.87, 2.30)	8.55 (7.64, 9.56)	152 (105, 220)	1024 (774, 1355)

CRM: cross-reactive material; DTPa-HBV-IPV: diphtheria-tetanus-acellular pertussis/hepatitis B/inactivated polio vaccine; DTPw-HBV: diphtheria-tetanus-whole-cell pertussis/hepatitis B vaccine; ELISA: enzyme-linked immunosorbent assay; GMC: geometric mean concentration; GMT: geometric mean titer; Hib: Haemophilus influenzae type B; IgG: immunoglobulin G; IPV: inactivated polio vaccine; MenC: meningococcal serogroup C; NS: not studied; OPA: opsonophagocytic activity; PCV7: 7-valent pneumococcal conjugate vaccine; PCV10: 10-valent pneumococcal conjugate vaccine; TT: tetanus toxoid.

^aImmune responses were measured 1-month post-primary and post-final dose using 22F-inhibition ELISA. In this assay, a reference antibody concentration of 0.2 μg/mL is equivalent to 0.35 μg/mL when using the non-22F ELISA at the World Health Organization reference laboratory [60,78].

^bFinnish, French, and Polish infants received 3 primary doses of PCV10 or PCV7 at 2, 3, and 4 months of age and a final dose at 12–18 months.

^cKorean infants received 3 primary doses of PCV10 or PCV7 at 2, 4, and 6 months and a final dose at 12–18 months of age, both coadministered with Hib vaccine.

^dFilipino infants received 3 primary doses of PCV10 or PCV7 at 6, 10, and 14 weeks of age and a final dose at 12–18 months of age. The final dose was coadministered with DTPw-HBV/Hib and poliovirus vaccines.

^ePolish infants received 3 primary doses of PCV10 or PCV7 at 2, 4, and 6 months of age and a final dose at 12–18 months of age. The final dose was co-administered with DTPw-HBV/Hib and poliovirus vaccines.

^fDanish, Norwegian, Slovakian, and Swedish infants received 3 primary doses of PCV10 at 2, 3, and 4 months of age and a final dose at 11 months of age.

^gGerman, Polish, and Spanish infants received either PCV10 coadministered with: (1) DTPa-HBV-IPV/Hib and MenC-CRM; (2) DTPaHBV-IPV/Hib and MenC-TT; (3) DTPa-HBV-IPV and Hib-MenC-TT; (4) or PCV7 coadministered with DTPa-HBV-IPV and Hib-MenC-TT at 2, 4, and 6 months of age with a final dose at 11–18 months of age.

^hInfants from a single center in the Netherlands received either: (1) PCV10 and DTPa-HBV-IPV/Hib; (2) PCV10 and DTPa-IPV/Hib; or (3) PCV7 at 2, 3, and 4 months of age.

ⁱGerman infants received 3 primary doses of PCV13 or PCV7 at 2, 3, and 4 months of age and a final dose at 11–12 months of age.

^jAmerican infants received 3 primary doses of PCV13 or PCV7 at 2, 3, and 4 months of age and a final dose at 12–15 months of age.

Figure 1. Immune responses specific for serotype 19A after vaccination with PCV10 or PCV13. (a) Anti-serotype 19A geometric mean concentrations from study NCT01616459 [86]. Children in Europe were administered PCV10 or PCV13 at 2, 3, and 4 months of age (primary series). Samples for immunogenicity analysis were taken before and 1 month after the primary vaccination series. Data adapted from GlaxoSmithKline study NTC0161459 [86]. (b) Anti-serotype 19A responses from study NTR3069. Children in the Netherlands were administered PCV10 or PCV13 at 2, 3, 4, (primary series) and 11 months (booster) of age. Samples for immunogenicity analyses were taken 1 week after the booster dose. Data adapted from van Westen et al [84] and Wijmenga-Monsuur et al [85].

ASCs: antibody-secreting cells; IgG: immunoglobulin G; OPA: opsonophagocytic activity assay; PBMCs: peripheral blood mononuclear cells; PCV10: 10-valent pneumococcal conjugate vaccine; PCV13: 13-valent pneumococcal conjugate vaccine.

Figure 2. Randomized controlled trials assessing the impact of PCVs on NP carriage related to serotype 19A or cross-reactive serotypes in (a) Israel, data adapted from Dagan et al. [117] (Dagan, Ron and Patterson, Scott; Comparative Immunogenicity and Efficacy of 13-Valent and 7-Valent Pneumococcal Conjugate Vaccines in Reducing Nasopharyngeal Colonization: A Randomized Double-Blind Trial, Clinical Infectious Diseases, 2013, Vol 57/Issue 7: 952–962, by permission of Oxford University Press); (b) the Netherlands, data adapted from van den Bergh et al [118]; and (c) Argentina/Panama/Colombia (COMPAS) [120].

NP: nasopharyngeal; PCV7: 7-valent pneumococcal conjugate vaccine; PCV10: 10-valent pneumococcal conjugate vaccine; PCV13: 13-valent pneumococcal conjugate vaccine.*Significant difference in carriage, PCV7 vs. PCV13. ^†Any serotype belonging to the same serogroup as the PCV10 vaccine serotypes, but different from vaccine serotypes.

Figure 3. Impact of PCV10 on serotype 19A carriage in a randomized controlled trial conducted in Finland; data adapted from Vesikari et al [105] and from GSK study report 112,595 [121]. (a) 3 + 1 regimen vs. control (hepatitis B virus vaccine or hepatitis A virus vaccine; NP swabs were collected before vaccine dose 1, 1 month after dose 3, before the booster dose, 3 months after the booster dose, and 10 months after the booster dose. (b) 2 + 1 regimen vs. control; NP swabs were collected before vaccine dose 1, 1 month after dose 2, before the booster dose, 3 months after the booster dose, and 10 months after the booster dose.

PCV10: 10-valent pneumococcal conjugate vaccine.

Table 2. Studies examining the effect of PCVs on serotype 19A.

Citation	Study location	Year after vaccine introduction	Variable measured (isolates, serotype 19A prevalence, or vaccine effectiveness)	Findings
Carriage/Colonization
PCV7/PCV13
Dagan et al. [117]	Israel	–	NP isolates from children aged ≤24 mo	PCV7 vaccinated = 22.9%
				PCV13 vaccinated = 12.6%
Lee et al. [95]	USA	1	NP isolates from children aged <7 y seen for well child or acute care visits	Decline in carriage in 2011 compared with 2009
Loughlin et al. [98]	USA	1–2	NP isolates from children aged <5 y seen for well child or urgent care visits	Year 1 = 3 per 100 children Year 2 = <1 per 100 children
Zucotti et al. [104]	Italy	1	NP isolates each from healthy children unimmunized, or vaccinated with PCV7 or PCV13 (5 September–6 December 2011)	Unimmunized = 9%
				PCV7 vaccinated = 12%
				PCV13 vaccinated = 0%
Cohen et al. [123]	France	1	NP isolates from children with AOM (October 2010–May 2011)	PCV7 vaccinated = 15.4% PCV13 vaccinated = 7.5% (P < 0.001)
Dunais et al. [96]	France	2	Serotype 19A prevalence	Pre-PCV13 (2008) = 15.5%
				Post-PCV13 (2012) = 6.5%
Desai et al [94]	USA	3	Serotype 19A prevalence	Pre-PCV13 (July–December 2010) = 25.8%
				Post-PCV13 (January–June 2013) = 3.0% (P < 0.0001)
PCV10
Prymula et al. [122]	Czech Republic	NA	Vaccine efficacy (NP isolates from healthy children 1 y after booster dose)	Vaccine efficacy (95% CI) for carriage of cross-reactive serotypes = 18.6% (−105.5%, 68.5%)
van den Bergh et al. [118]	The Netherlands	NA	Serotype 19A prevalence (NP swabs from children aged <2 y)	Serotype 19A was predominant colonizing serotype.
				PCV7 vaccinated = 30.8% across all visits;
				PCV10-vaccinated = 28.1% across all visits
Vesikari et al. [105,121]	Finland	NA	NP isolates from children aged <22 mo	Statistically significant decrease in serotype 19A carriage in children 18–22 mo of age vaccinated on a 3 + 1 schedule vs. nonvaccinated children
				Statistically significant reductions not observed in other age groups or in any age group vaccinated on a 2 + 1 schedule
Hammitt et al. [102]	Kenya	2	NP isolates from residents of Kilifi, Kenya before and after vaccine introduction	Serotype 19A carriage prevalence increased in the period after vaccine introduction
Wyllie et al. [119]	The Netherlands	1–2	Serotype 19A carriage	Nonstatistically significant reduction (P = 0.22) in serotype 19A carriage in children vaccinated with PCV10
Brandileone et al. [91]	Brazil	3	NP isolates from children 12–23 mo of age pre- and post-PCV10 introduction	No significant change in carriage of serotype 19A (P = 0.4562)
PCV7/PCV10
Best et al. [97]	New Zealand	3	NP and middle ear fluid isolates for 2 cohorts of children aged <36 mo comparing the PCV7 era (2011) with the PCV10 era (2014)	Serotype 19A was the most prominent S pneumoniae serotype in NP samples in the PCV10 era
Mucosal Disease
PCV7/PCV13
Ben-Shimol et al. [124]	Israel	3	Serotype 19A isolates from middle ear fluid cultures from children aged <2 y with otitis media (July 2004–June 2013)	IRR (95% CI): PCV13 period vs. PCV7 period = 0.09 (0.04, 0.20)
				PCV13 period vs. pre-PCV7 period = 0.15 (0.06, 0.35)
Olarte et al. [51]	USA	3	Serotype 19A isolates in patients with chronic sinusitis who underwent endoscopic sinus surgery	Pre-PCV13 (2008–2010) = 38% Post-PCV13 (2011–2013) = 11% (P = 0.007)
Kaplan et al. [53]	USA	1–3	Serotype 19A isolates from middle ear or mastoid cultures	2011 = 33.6% of isolates
				2013 = 10.2% of isolates
PCV7/PCV10
Best et al. [97]	New Zealand	3	Serotype 19A isolates from middle ear fluid for 2 cohorts of children aged <36 mo comparing the PCV7 era (2011) with the PCV10 era (2014)	Serotype 19A was the most prominent S pneumoniae serotype in middle ear fluid in the PCV10 era
Invasive Pneumococcal Disease
PCV7/PCV13
Olarte et al. [125]	USA	3	Serotype 19A isolates from pediatric patients with pneumococcal meningitis	Pre-PCV13 = 27.03%; Post-PCV13 = 14.93% (P = 0.08)
Kaplan et al. [126]	USA	1–2	Serotype 19A prevalence	Pre-PCV13 (2007–2009) = 40.07%
				Post-PCV13 (2011) = 28.57%
Iroh Tam et al. [127]	USA	2	Serotype 19A prevalence	Pre-PCV13 (2007–2009) = 39.88%;
				Post-PCV13 (2010–2012) = 20.00% (P < 0.0001)
Moore et al. [128]	USA	3	Serotype 19A prevalence	Age <5 y  Pre-PCV13 (2009–2010) = 52.84%
				Post-PCV13 (2012–2013) = 11.11%
				Age 5–17 y Pre-PCV13 = 16.67%
				Post-PCV13 = 13.73%
				Age 18–49 y Pre-PCV13 = 22.93%
				Post-PCV13 = 10.63%
				Age 50–64 y Pre-PCV13 = 20.14%
				Post-PCV13 = 10.42%
				Age ≥65 y Pre-PCV13 = 20.00%
				Post-PCV13 = 7.75%
Farnham et al. [129]	USA	2	Serotype 19A prevalence	Change in IPD incidence from pre-PCV13 period to post-PCV13 period: −79.69%, P = 0.001
Moore et al. [130]	USA	1–4	Vaccine effectiveness (95% CI) among children aged 2–59 mo	85.6% (70.6%, 93.5%)
Demczuk et al. [112]	Canada	2	IPD isolates	Pre-PCV13 (2010) = 19.12%;
				Post-PCV13 (2012) = 13.89% (P < 0.001)
Andrews et al. [131]	England, Wales, Northern Ireland	3–5	Vaccine effectiveness (95% CI)	67% (33%, 84%)
Waight et al. [132]	England and Wales	4	Serotype 19A prevalence	Age <5 y = 0.09 (0.03, 0.25) (P < 0.0001) Age 5–64 y = 0.46 (0.35, 0.68) (P < 0.0001) Age ≥65 y = 0.35 (0.25, 0.47) (P < 0.0001)
			IRR (95% CI) between post-PCV13 period and pre-PCV13 period
Harboe et al. [133]	Denmark	3	Serotype 19A prevalence Pre-PCV7 (January 2000–December 2007) PCV7 (January 2008–December 2010) Post-PCV13 (January 2011–December 2013)	Decline in incidence post-PCV13 toward pre-PCV7 levels
Ben-Shimol et al. [134]	Israel	2–3	IPD incidence (per 100,000) in children aged ≤5 y	Pre-PCV7 period (2004–2008) = 5.1 PCV7 period (2010–2011) = 5.0 Post-PCV13 period (2012–2013) = 1.6 (both differences P < 0.05)
Wei et al. [135]	Taiwan	1	IPD incidence (per 100,000 person-years) in children aged <5 y	2008–2010 = 1.7 2011–2012 = 10.3 2013 = 5.6
Von Gottberg et al. [136]	South Africa	1	IPD incidence (per 100,000 person-years) in children aged <2 y	70% decrease from pre-PCV7 period (2005–2008) to 1 y after PCV13 introduction (2012)
Lepoutre et al. [137]	France	2	IPD incidence	83% decrease from pre-PCV13 period (2008–2009) to post-PCV13 period (2012)
Picazo et al. [138]	Spain	2	IPD incidence (per 100,000 persons) Pre-PCV13 period (2007–2010) Post-PCV13 period (2011–2012)	Age <12 mo Pre-PCV13 period = 16.47Post-PCV13 period = 2.72 Age ≥12 to <24 mo Pre-PCV13 period = 16.73 Post-PCV13 period = 2.66 Age ≥24 to <60 mo Pre-PCV13 period = 3.99 Post-PCV13 period =0.45
Deceuninck et al. [139]	Canada	8 PCV7 = 3 PCV10 = 2 PCV13 = 2	Vaccine effectiveness (95% CI) in children aged 2–59 mo	PCV7 = 42% (−9%, 69%) (P = 0.093); PCV13 = 74% (11%, 92%) (P = 0.032)
PCV10
Domingues et al. [140]	Brazil	1–2	Vaccine effectiveness (95% CI) in children aged ≥2 mo	82.2% (10.7%, 96.4%)
Jokinen et al. [141]	Finland	1–3	Vaccine effectiveness (95% CI) in children aged 3–42 mo	2011–2013 for 19A = 62% (20%, 85%) 2013 for 6A+19A = 8% (–107%, 62%)
Deceuninck et al. [139]	Canada	8 PCV7 = 3 PCV10 = 2 PCV13 = 2	Vaccine effectiveness (95% CI) in children aged 2–59 mo	71% (24%, 89%) (P = 0.013)

AOM: acute otitis media; IPD: invasive pneumococcal disease; IRR: incidence rate ratio; NA: not applicable; NP: nasopharyngeal; PCV7: 7-valent pneumococcal conjugate vaccine; PCV10: 10-valent pneumococcal conjugate vaccine; PCV13: 13-valent pneumococcal conjugate vaccine.

Figure 4. Surveillance data for serotype 19A invasive pneumococcal disease in individuals <5 years or ≥5 years of age from countries that introduced PCV7, PCV10, and PCV13 into their national immunization programs. Data for Canada (Quebec; panels a and c) are adapted from the National Institute for Health and Welfare [142]. New Zealand data (panels b and d) are adapted from Public Health Surveillance [171,174]. Data for children <5 years of age are shown in panels a and b, and for individuals ≥5 years old in panels c and d.

IPD: invasive pneumococcal disease; PCV7: 7-valent pneumococcal conjugate vaccine; PCV10: 10-valent pneumococcal conjugate vaccine; PCV13: 13-valent pneumococcal conjugate vaccine.

Figure 5. Surveillance data for serotype 19A invasive pneumococcal disease  from countries that introduced only PCV10 into their national immunization programs. Data for Finland (panels a and d) are adapted from National Institute of Health and Welfare [141,146]; data for Brazil (panels b and e) are adapted from Cassiolato et al [163]. Data for Chile (panels c and f) are adapted from the Institute of Public Health [144]. Data for children <5 years of age are shown in panels a and b, and for individuals ≥5 years old in panels d and e. Panels c and f (Chile) show data for individuals <2 years and ≥2 years of age, respectively.

IPD: invasive pneumococcal disease; PCV10: 10-valent pneumococcal conjugate vaccine.

Figure 6. Surveillance data for serotype 19A invasive pneumococcal disease in individuals <5 years or ≥5 years of age in countries that switched from PCV7 to PCV13 in their national immunization programs. Data for the USA (panels a and c) are from the Centers for Disease Control and Prevention Active Bacterial Core Surveillance and adapted from Moore et al. [128]. Data for Norway (panels b and d) are from the Norwegian Institute of Public Health and adapted from Steens et al [147]. Data for children <5 years of age are shown in panels a and b, and for individuals ≥5 years old in panels c and d.

IPD: invasive pneumococcal disease; PCV7: 7-valent pneumococcal conjugate vaccine; PCV13: 13-valent pneumococcal conjugate vaccine.

Vesikari T, Wysocki J, Chevallier B, et al. Immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) compared to the licensed 7vCRM vaccine. Pediatr Infect Dis J. 2009;28:S66–76.

 PubMed Web of Science ®Google Scholar

Kim CH, Kim JS, Cha SH, et al. Response to primary and booster vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in Korean infants. Pediatr Infect Dis J. 2011;30:e235–43.

 PubMed Web of Science ®Google Scholar

Bermal N, Szenborn L, Chrobot A, et al. The 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) coadministered with DTPw-HBV/Hib and poliovirus vaccines: assessment of immunogenicity. Pediatr Infect Dis J. 2009;28:S89–96.

 PubMed Web of Science ®Google Scholar

Bermal N, Szenborn L, Edison A, et al. Safety and immunogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine coadministered with DTPw-HBV/Hib and poliovirus vaccines. Pediatr Infect Dis J. 2011;30:69–72.

 PubMed Web of Science ®Google Scholar

GlaxoSmithKline. Clinical Study Report for Study 105539. [ cited 2017 Aug 4]. Available from: http://www.gsk-clinicalstudyregister.com/study/105539#csr

 Google Scholar

Wysocki J, Tejedor JC, Grunert D, et al. Immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when coadministered with different neisseria meningitidis serogroup C conjugate vaccines. Pediatr Infect Dis J. 2009;28:S77–88.

 PubMed Web of Science ®Google Scholar

van den Bergh MR, Spijkerman J, Francois N, et al. Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine and DTPa-IPV-Hib when coadministered as a 3-dose primary vaccination schedule in The Netherlands: a randomized controlled trial. Pediatr Infect Dis J. 2011;30:e170–8.

 PubMed Web of Science ®Google Scholar

Kieninger DM, Kueper K, Steul K, et al. Safety, tolerability, and immunologic noninferiority of a 13-valent pneumococcal conjugate vaccine compared to a 7-valent pneumococcal conjugate vaccine given with routine pediatric vaccinations in Germany. Vaccine. 2010;28:4192–4203.

 PubMed Web of Science ®Google Scholar

Yeh SH, Gurtman A, Hurley DC, et al. Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in infants and toddlers. Pediatrics. 2010;126:e493–505.

 PubMed Web of Science ®Google Scholar

Expert WHO Committee on Biological Standarization. WHO TechnicalReport Series 927. [cited 2017 Aug 4]. Available from: http://www.who.int/biologicals/WHO_TRS_%20927%20full%20tex.pdf

 Google Scholar

Henckaerts I, Goldblatt D, Ashton L, et al. Critical differences between pneumococcal polysaccharide enzyme-linked immunosorbent assays with and without 22F inhibition at low antibody concentrations in pediatric sera. Clin Vaccine Immunol. 2006;13:356–360.

 Google Scholar

GlaxoSmithKline. Clinical Study Report for study 116485. [ cited 2017 Aug 4]. Available from: http://www.gsk-clinicalstudyregister.com/study/116485?study_ids=116485#rs

 Google Scholar

Van Westen E, Wijmenga-Monsuur AJ, Van Dijken HH, et al. Differential B-cell memory around the 11-month booster in children vaccinated with a 10- or 13-valent pneumococcal conjugate vaccine. Clin Infect Dis. 2015;61:342–349.

 PubMed Web of Science ®Google Scholar

Wijmenga-Monsuur AJ, van Westen E, Knol MJ, et al. Direct comparison of immunogenicity induced by 10- or 13-valent pneumococcal conjugate vaccine around the 11-month booster in Dutch infants. PLoS One. 2015;10:e0144739.

 Google Scholar

Dagan R, Patterson S, Juergens C, et al. Comparative immunogenicity and efficacy of 13-valent and 7-valent pneumococcal conjugate vaccines in reducing nasopharyngeal colonization: a randomized double-blind trial. Clin Infect Dis. 2013;57:952–962.

 PubMed Web of Science ®Google Scholar

van den Bergh MR, Spijkerman J, Swinnen KM, et al. Effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine on nasopharyngeal bacterial colonization in young children: a randomized controlled trial. Clin Infect Dis. 2013;56:e30–9.

 PubMed Web of Science ®Google Scholar

GlaxoSmithKline. COMPAS: a phase III study to demonstrate efficacy of GSK Biologicals’ 10-valent pneumococcal vaccine (GSK1024850A) against community acquired pneumonia and acute otitis media. [ cited 2017 Aug 4]. Available from: http://www.gsk-clinicalstudyregister.com/study/109563#rs

 Google Scholar

Vesikari T, Forsten A, Seppa I, et al. Effectiveness of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugated vaccine (PHiD-CV) against carriage and acute otitis media-a double-blind randomized clinical trial in Finland. J Pediatric Infect Dis Soc. 2016;5:237–248. DOI: 10.1093/jpids/piw010

 PubMed Web of Science ®Google Scholar

GlaxoSmithKline. Clinical study report for study 112595. Impact on nasopharyngeal carriage, acute otitis media, immunogenicity and safety of GSK Biologicals pneumococcal vaccine 1024850A. [ cited 2017 Aug 4]. Available from: https://www.gsk-clinicalstudyregister.com/study/112595?study_ids=112595#csr

 Google Scholar

Lee GM, Kleinman K, Pelton SI, et al. Impact of 13-valent pneumococcal conjugate vaccination on carriage in young children in Massachusetts. J Pediatric Infect Dis Soc. 2014;3:23–32.

 PubMedGoogle Scholar

Loughlin AM, Hsu K, Silverio AL, et al. Direct and indirect effects of PCV13 on nasopharyngeal carriage of PCV13 unique pneumococcal serotypes in Massachusetts’ children. Pediatr Infect Dis J. 2014;33:504–510.

 PubMed Web of Science ®Google Scholar

Zuccotti G, Mameli C, Daprai L, et al. Serotype distribution and antimicrobial susceptibilities of nasopharyngeal isolates of Streptococcus pneumoniae from healthy children in the 13-valent pneumococcal conjugate vaccine era. Vaccine. 2014;32:527–534.

 PubMed Web of Science ®Google Scholar

Cohen R, Levy C, Bingen E, et al. Impact of 13-valent pneumococcal conjugate vaccine on pneumococcal nasopharyngeal carriage in children with acute otitis media. Pediatr Infect Dis J. 2012;31:297–301.

 PubMed Web of Science ®Google Scholar

Dunais B, Bruno P, Touboul P, et al. Impact of the 13-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae among children attending group daycare in southeastern France. Pediatr Infect Dis J. 2015;34:286–288.

 PubMed Web of Science ®Google Scholar

Desai AP, Sharma D, Crispell EK, et al. Decline in pneumococcal nasopharyngeal carriage of vaccine serotypes after the introduction of the 13-valent pneumococcal conjugate vaccine in children in Atlanta, Georgia. Pediatr Infect Dis J. 2015;34:1168–1174.

 PubMed Web of Science ®Google Scholar

Prymula R, Habib A, Francois N, et al. Immunological memory and nasopharyngeal carriage in 4-year-old children previously primed and boosted with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with or without concomitant prophylactic paracetamol. Vaccine. 2013;31:2080–2088.

 PubMed Web of Science ®Google Scholar

Hammitt LL, Akech DO, Morpeth SC, et al. Population effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and non-typeable Haemophilus influenzae in Kilifi, Kenya: findings from cross-sectional carriage studies. Lancet Glob Health. 2014;2:e397–405.

 PubMed Web of Science ®Google Scholar

Wyllie AL, Wijmenga-Monsuur AJ, van Houten MA, et al. Molecular surveillance of nasopharyngeal carriage of Streptococcus pneumoniae in children vaccinated with conjugated polysaccharide pneumococcal vaccines. Sci Rep. 2016;6:23809.

 PubMed Web of Science ®Google Scholar

Brandileone MC, Zanella RC, Almeida SC, et al. Effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and haemophilus influenzae among children in Sao Paulo, Brazil. Vaccine. 2016;34:5604–5611.

 PubMed Web of Science ®Google Scholar

Best EJ, Walls T, Souter M, et al. Pneumococcal vaccine impact on otitis media microbiology: a New Zealand cohort study before and after the introduction of PHiD-CV10 vaccine. Vaccine. 2016. DOI:10.1016/j.vaccine.2016.05.041

 PubMed Web of Science ®Google Scholar

Ben-Shimol S, Givon-Lavi N, Leibovitz E, et al. Near-elimination of otitis media caused by 13-valent pneumococcal conjugate vaccine (PCV) serotypes in southern Israel shortly after sequential introduction of 7-valent/13-valent PCV. Clin Infect Dis. 2014;59:1724–1732.

 PubMed Web of Science ®Google Scholar

Olarte L, Hulten KG, Lamberth L, et al. Impact of the 13-valent pneumococcal conjugate vaccine on chronic sinusitis associated with Streptococcus pneumoniae in children. Pediatr Infect Dis J 2014;33:1033–1036.

 PubMed Web of Science ®Google Scholar

Kaplan SL, Center KJ, Barson WJ, et al. Multicenter surveillance of Streptococcus pneumoniae isolates from middle ear and mastoid cultures in the 13-valent pneumococcal conjugate vaccine era. Clin Infect Dis 2015;60:1339–1345.

 PubMed Web of Science ®Google Scholar

Olarte L, Barson WJ, Barson RM, et al. Impact of the 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in US children. Clin Infect Dis. 2015;61:767–775.

 PubMed Web of Science ®Google Scholar

Kaplan SL, Barson WJ, Lin PL, et al. Early trends for invasive pneumococcal infections in children after the introduction of the 13-valent pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2013;32:203–207.

 PubMed Web of Science ®Google Scholar

Iroh Tam PY, Madoff LC, Coombes B, et al. Invasive pneumococcal disease after implementation of 13-valent conjugate vaccine. Pediatrics. 2014;134:210–217.

 PubMed Web of Science ®Google Scholar

Moore MR, Link-Gelles R, Schaffner W, et al. Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance. Lancet Infect Dis. 2015;15:301–309.

 PubMed Web of Science ®Google Scholar

Farnham AC, Zimmerman CM, Papadouka V, et al. Invasive pneumococcal disease following the introduction of 13-valent conjugate vaccine in children in New York City from 2007 to 2012. JAMA Pediatr. 2015;169:646–652.

 PubMed Web of Science ®Google Scholar

Moore MR, Link-Gelles R, Schaffner W, et al. Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease in children in the USA: a matched case-control study. Lancet Respir Med. 2016;4:399–406.

 PubMed Web of Science ®Google Scholar

Demczuk WH, Martin I, Griffith A, et al. Serotype distribution of invasive Streptococcus pneumoniae in Canada after the introduction of the 13-valent pneumococcal conjugate vaccine, 2010-2012. Can J Microbiol. 2013;59:778–788.

 PubMed Web of Science ®Google Scholar

Andrews NJ, Waight PA, Burbidge P, et al. Serotype-specific effectiveness and correlates of protection for the 13-valent pneumococcal conjugate vaccine: a postlicensure indirect cohort study. Lancet Infect Dis. 2014;14:839–846.

 PubMed Web of Science ®Google Scholar

Waight PA, Andrews NJ, Ladhani SN, et al. Effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study. Lancet Infect Dis. 2015;15:535–543.

 PubMed Web of Science ®Google Scholar

Harboe ZB, Dalby T, Weinberger DM, et al. Impact of 13-valent pneumococcal conjugate vaccination in invasive pneumococcal disease incidence and mortality. Clin Infect Dis. 2014;59:1066–1073.

 PubMed Web of Science ®Google Scholar

Ben-Shimol S, Greenberg D, Givon-Lavi N, et al. Early impact of sequential introduction of 7-valent and 13-valent pneumococcal conjugate vaccine on IPD in Israeli children <5 years: an active prospective nationwide surveillance. Vaccine. 2014;32:3452–3459.

 PubMed Web of Science ®Google Scholar

Wei SH, Chiang CS, Chiu CH, et al. Pediatric invasive pneumococcal disease in Taiwan following a national catch-up program with the 13-valent pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2015;34:e71–7.

 PubMed Web of Science ®Google Scholar

von Gottberg A, de Gouveia L, Tempia S, et al. Effects of vaccination on invasive pneumococcal disease in South Africa. N Engl J Med. 2014;371:1889–1899.

 PubMed Web of Science ®Google Scholar

Lepoutre A, Varon E, Georges S, et al. Impact of the pneumococcal conjugate vaccines on invasive pneumococcal disease in France, 2001-2012. Vaccine. 2015;33:359–366.

 PubMed Web of Science ®Google Scholar

Picazo J, Ruiz-Contreras J, Casado-Flores J, et al. Expansion of serotype coverage in the universal pediatric vaccination calendar: short-term effects on age- and serotype-dependent incidence of invasive pneumococcal clinical presentations in Madrid, Spain. Clin Vaccine Immunol. 2013;20:1524–1530.

 PubMed Web of Science ®Google Scholar

Deceuninck G, De Serres G, Boulianne N, et al. Effectiveness of three pneumococcal conjugate vaccines to prevent invasive pneumococcal disease in Quebec, Canada. Vaccine. 2015;33:2684–2689.

 PubMed Web of Science ®Google Scholar

Domingues CM, Verani JR, Montenegro Renoiner EI, et al. Effectiveness of ten-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in Brazil: a matched case-control study. Lancet Respir Med. 2014;2:464–471.

 PubMed Web of Science ®Google Scholar

Jokinen J, Rinta-Kokko H, Siira L, et al. Impact of ten-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in Finnish children–a population-based study. PLoS One. 2015;10:e0120290.

 PubMed Web of Science ®Google Scholar

Lefebvre B. Programme de surveillance du pneumocoque: rapport 2013. [ cited 2017 Aug 4]. Available from: https://www.inspq.qc.ca/pdf/publications/1946_Programme_Surveillance_Pneumocoque.pdf

 Google Scholar

Institute of Environmental Science and Research Ltd (ESR). Invasive pneumococcal disease in New Zealand. Wellington (NZ): Ministry of Health; 2014. [ cited 2017 Aug 4]. Available from https://surv.esr.cri.nz/PDF_surveillance/IPD/2014/2014IPDAnnualReport.pdf.

 Google Scholar

Borman A, Heffernan H. Invasive pneumococcal disease quarterly report. October-December 2015. [ cited 2017 Aug 4]. Available from: https://surv.esr.cri.nz/surveillance/IPD.php

 Google Scholar

National Institute for Health and Welfare. Incidence of invasive pneumococcal disease in Finland. [ cited 2017 Aug 4]. Available from: https://www.thl.fi/en/web/thlfi-en/topics/information-packages/incidence-of-invasive-pneumococcal-disease-in-finland

 Google Scholar

Cassiolato A, Almeida S, Guerra M, et al. Changes in invasive Streptococcus pneumoniae serotype (Spn) 19A after introduction of 10-valent pneumococcal conjugate vaccine (PCV10) in Brazil. Presented at: 9th Wold Congress of the World Society for Pediatric Infectious Diseases (WSPID); 2015; Rio de Janiero, Brazil

 Google Scholar

Instituto de Salud Publica de Chile. Boletin Instituto de Salud Publica de Chile. Julio 2015. Vigilancia de laboratorio de Streptococcus pneumoniae procedente de enfermedad invasora. Chile, 2007-2015. [cited 2017 Aug 4]. Available from: http://www.ispch.cl/sites/default/files/Boletín%20de%20Vigilancia%20de%20Laboratorio%20de%20Streptococcus%20pneumoniae.pdf

 Google Scholar

Steens A, Bergsaker MA, Aaberge IS, et al. Prompt effect of replacing the 7-valent pneumococcal conjugate vaccine with the 13-valent vaccine on the epidemiology of invasive pneumococcal disease in Norway. Vaccine. 2013;31:6232–6238.

 PubMed Web of Science ®Google Scholar