Prevailing and Emerging Pediatric Pneumococcal Serotypes
Prevailing and Emerging Pediatric Pneumococcal Serotypes
Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths among children younger than 5 years of age worldwide. The 7-valent pneumococcal conjugate vaccine (PCV7) is currently licensed in more than 90 countries and has contributed to significant declines in the incidence of invasive pneumococcal disease (IPD). Recent studies report an increased incidence of IPD caused by non-PCV7 vaccine serotypes (NVTs). Seroepidemiology of IPD caused by NVTs following the introduction of PCV7 is of interest, and this article provides a comprehensive global summary of the prevailing and emerging serotypes causing IPD in children. Currently, globally emerging or persistent NVTs include serotypes 1, 3, 5, 6A, 7F and 19A. Serotypes included in the recently licensed 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) account for pneumococcal disease burdens in most developed countries of 65–85% and 80–90%, respectively. The seroprevalence of NVTs after widespread use of PCV10 and PCV13 requires ongoing monitoring.
Streptococcus pneumoniae is implicated in multiple diseases in infants and children, including invasive infections (e.g., meningitis, septicemia, bacteremia and bacteremic pneumonia) and mucosal infections (e.g., otitis media, sinusitis and nonbacteremic pneumonia).
The 7-valent pneumococcal conjugate vaccine (PCV7), which includes serotypes 4, 6B, 9V, 14, 18C, 19F and 23F, was licensed in the USA in 2000 and in Europe in 2001. By March 2010, PCV7 was licensed in more than 90 of the 193 member states of the WHO and was included in the routine or national immunization programs (NIPs) or was widely used in more than 40 of these countries [Pfizer, Data On File]. In 13 countries, the vaccine was provided only to high-risk individuals, such as the chronically ill, HIV-positive, or immunocompromised.
Benefits of PCV7 include: reduction in the incidence of invasive pneumococcal disease (IPD) due to PCV7 vaccine serotypes (VTs) in the USA, Canada, Australia, the UK, France, Germany, Norway, Spain, The Netherlands and Belgium; reduction in antimicrobial resistance among IPD isolates (for a review, see); fewer outpatient visits for otitis media; fewer tympanostomy tube procedures; and decreases in hospitalizations for pneumonia. Age groups that do not constitute the target population of the vaccine have also benefited from PCV7 through the phenomenon of indirect (herd) protection, resulting in decreases in incidence of disease caused by VTs in the nonvaccinated age groups.
Two pneumococcal conjugate vaccines (PCVs) designed to broaden coverage have been licensed. The 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PCV10) contains serotypes 1, 4, 5, 6B, 7F, 9V, 14 and 23F conjugated to nontypeable H. influenzae protein D, plus serotype 18C conjugated to tetanus toxoid and serotype 19F conjugated to diphtheria toxoid. The 13-valent pneumococcal conjugate vaccine (PCV13) contains the PCV7 serotypes plus serotypes 1, 3, 5, 6A, 7F and 19A, conjugated to cross-reactive material CRM197. In addition, 9- and 11-valent investigational PCVs were developed, but not licensed, including a 9-valent PCV that contained serotypes 1 and 5 in addition to the seven serotypes in PCV7, and an 11-valent PCV that contained the additional serotypes 1, 5, 3 and 7F using the protein D carrier, which was the prototype of PCV10.
Some studies conducted after the introduction of PCV7 documented an increase in pneumococcal disease caused by non-PCV7 serotypes (NVTs). These included studies conducted by the US CDC, Kaplan et al. and Muñoz-Almagro et al., and they resulted in considerable interest in the epidemiology and burden of disease caused by NVTs, in particular the extent to which the use of PCV7 contributes to so-called 'serotype replacement.' Other factors, such as antibiotic pressure, have been identified as contributors to the emergence of pneumococcal clones (for a review, see), and an increase in NVTs has been seen in countries with no or only limited access to conjugate vaccines. Over the past few years, reviews have summarized various aspects of regional and global pneumococcal serotype distribution and IPD incidence in children. As pneumococcal serotype distribution and IPD incidence change over time, updated global surveillance data provide important information on the current status of pneumococcal seroepidemiology.
This article summarizes recent worldwide data on the burden of disease and serotype distribution prior to the implementation of PCV10 and PCV13. Data were available from 63 countries throughout Europe, the Middle East and North Africa, Africa, Latin America, the Asia–Pacific region and North America. Data for indigenous and nonindigenous populations are presented for the USA and Australia. Changes in incidence of antibiotic resistance are not reported. Current status of licensure, NIPs, vaccination schedules and uptake are shown in Supplementary Table 1. Burden of IPD by country is shown in Supplementary Table 2. Supplementary Table 3 shows the frequency of serotype distribution and serotype coverage. Figure 1 shows cumulative worldwide distribution of serotypes causing pediatric IPD in global regions for the period prior to introduction of PCV7 into NIPs; Figure 2 shows the cumulative worldwide distribution of serotypes causing pediatric IPD in global regions for the period following introduction of PCV7 into NIPs for Europe and North America. Changes in serotype distribution before and after licensure of PCV7 are described within countries within regions.
(Enlarge Image)
Figure 1.
Cumulative distribution, by global regions, of serotypes causing pediatric invasive pneumococcal disease for the 13 serotypes in the 13-valent pneumococcal conjugate vaccine (PCV13) and an aggregate estimate for other (non-PCV13) serotypes, prior to the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Data are representative of all pediatric age groups. Because this is not a meta-analysis, no effort was made to weight or model the data to create the figure; the figure is intended instead for illustrative purposes.
a: Serotype is present in PCV7; b: serotype is present in PCV10; c: serotype is present in PCV13.
(Enlarge Image)
Figure 2.
Cumulative distribution, by global regions, of serotypes causing pediatric invasive pneumococcal disease for the 13 serotypes in the 13-valent pneumococcal conjugate vaccine (PCV13) and an aggregate estimate for other (non-PCV13) serotypes, post-introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Data were available for Europe and North America. Data are representative of all pediatric age groups. Because this is not a meta-analysis, no effort was made to weight or model the data to create the figure; the figure is intended instead for illustrative purposes.
a: Serotype is present in PCV7; b: serotype is present in PCV10; c: serotype is present in PCV13.
Abstract and Introduction
Abstract
Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths among children younger than 5 years of age worldwide. The 7-valent pneumococcal conjugate vaccine (PCV7) is currently licensed in more than 90 countries and has contributed to significant declines in the incidence of invasive pneumococcal disease (IPD). Recent studies report an increased incidence of IPD caused by non-PCV7 vaccine serotypes (NVTs). Seroepidemiology of IPD caused by NVTs following the introduction of PCV7 is of interest, and this article provides a comprehensive global summary of the prevailing and emerging serotypes causing IPD in children. Currently, globally emerging or persistent NVTs include serotypes 1, 3, 5, 6A, 7F and 19A. Serotypes included in the recently licensed 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) account for pneumococcal disease burdens in most developed countries of 65–85% and 80–90%, respectively. The seroprevalence of NVTs after widespread use of PCV10 and PCV13 requires ongoing monitoring.
Introduction
Streptococcus pneumoniae is implicated in multiple diseases in infants and children, including invasive infections (e.g., meningitis, septicemia, bacteremia and bacteremic pneumonia) and mucosal infections (e.g., otitis media, sinusitis and nonbacteremic pneumonia).
The 7-valent pneumococcal conjugate vaccine (PCV7), which includes serotypes 4, 6B, 9V, 14, 18C, 19F and 23F, was licensed in the USA in 2000 and in Europe in 2001. By March 2010, PCV7 was licensed in more than 90 of the 193 member states of the WHO and was included in the routine or national immunization programs (NIPs) or was widely used in more than 40 of these countries [Pfizer, Data On File]. In 13 countries, the vaccine was provided only to high-risk individuals, such as the chronically ill, HIV-positive, or immunocompromised.
Benefits of PCV7 include: reduction in the incidence of invasive pneumococcal disease (IPD) due to PCV7 vaccine serotypes (VTs) in the USA, Canada, Australia, the UK, France, Germany, Norway, Spain, The Netherlands and Belgium; reduction in antimicrobial resistance among IPD isolates (for a review, see); fewer outpatient visits for otitis media; fewer tympanostomy tube procedures; and decreases in hospitalizations for pneumonia. Age groups that do not constitute the target population of the vaccine have also benefited from PCV7 through the phenomenon of indirect (herd) protection, resulting in decreases in incidence of disease caused by VTs in the nonvaccinated age groups.
Two pneumococcal conjugate vaccines (PCVs) designed to broaden coverage have been licensed. The 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PCV10) contains serotypes 1, 4, 5, 6B, 7F, 9V, 14 and 23F conjugated to nontypeable H. influenzae protein D, plus serotype 18C conjugated to tetanus toxoid and serotype 19F conjugated to diphtheria toxoid. The 13-valent pneumococcal conjugate vaccine (PCV13) contains the PCV7 serotypes plus serotypes 1, 3, 5, 6A, 7F and 19A, conjugated to cross-reactive material CRM197. In addition, 9- and 11-valent investigational PCVs were developed, but not licensed, including a 9-valent PCV that contained serotypes 1 and 5 in addition to the seven serotypes in PCV7, and an 11-valent PCV that contained the additional serotypes 1, 5, 3 and 7F using the protein D carrier, which was the prototype of PCV10.
Some studies conducted after the introduction of PCV7 documented an increase in pneumococcal disease caused by non-PCV7 serotypes (NVTs). These included studies conducted by the US CDC, Kaplan et al. and Muñoz-Almagro et al., and they resulted in considerable interest in the epidemiology and burden of disease caused by NVTs, in particular the extent to which the use of PCV7 contributes to so-called 'serotype replacement.' Other factors, such as antibiotic pressure, have been identified as contributors to the emergence of pneumococcal clones (for a review, see), and an increase in NVTs has been seen in countries with no or only limited access to conjugate vaccines. Over the past few years, reviews have summarized various aspects of regional and global pneumococcal serotype distribution and IPD incidence in children. As pneumococcal serotype distribution and IPD incidence change over time, updated global surveillance data provide important information on the current status of pneumococcal seroepidemiology.
This article summarizes recent worldwide data on the burden of disease and serotype distribution prior to the implementation of PCV10 and PCV13. Data were available from 63 countries throughout Europe, the Middle East and North Africa, Africa, Latin America, the Asia–Pacific region and North America. Data for indigenous and nonindigenous populations are presented for the USA and Australia. Changes in incidence of antibiotic resistance are not reported. Current status of licensure, NIPs, vaccination schedules and uptake are shown in Supplementary Table 1. Burden of IPD by country is shown in Supplementary Table 2. Supplementary Table 3 shows the frequency of serotype distribution and serotype coverage. Figure 1 shows cumulative worldwide distribution of serotypes causing pediatric IPD in global regions for the period prior to introduction of PCV7 into NIPs; Figure 2 shows the cumulative worldwide distribution of serotypes causing pediatric IPD in global regions for the period following introduction of PCV7 into NIPs for Europe and North America. Changes in serotype distribution before and after licensure of PCV7 are described within countries within regions.
(Enlarge Image)
Figure 1.
Cumulative distribution, by global regions, of serotypes causing pediatric invasive pneumococcal disease for the 13 serotypes in the 13-valent pneumococcal conjugate vaccine (PCV13) and an aggregate estimate for other (non-PCV13) serotypes, prior to the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Data are representative of all pediatric age groups. Because this is not a meta-analysis, no effort was made to weight or model the data to create the figure; the figure is intended instead for illustrative purposes.
a: Serotype is present in PCV7; b: serotype is present in PCV10; c: serotype is present in PCV13.
(Enlarge Image)
Figure 2.
Cumulative distribution, by global regions, of serotypes causing pediatric invasive pneumococcal disease for the 13 serotypes in the 13-valent pneumococcal conjugate vaccine (PCV13) and an aggregate estimate for other (non-PCV13) serotypes, post-introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Data were available for Europe and North America. Data are representative of all pediatric age groups. Because this is not a meta-analysis, no effort was made to weight or model the data to create the figure; the figure is intended instead for illustrative purposes.
a: Serotype is present in PCV7; b: serotype is present in PCV10; c: serotype is present in PCV13.