Summary of key points

WHO Position Paper on

Pneumococcal conjugate
vaccines in infants and
children under 5 years of
age– February 2019

Published in the Weekly Epidemiological Record on 22 Febuary 2019

 Background
• Pneumococcal infections can lead to serious invasive diseases such as meningitis, septicaemia and
pneumonia, as well as milder but more common illnesses such as sinusitis and otitis media.

• There are > 90 known serotypes of S. pneumoniae. The distribution of serotypes that cause disease
varies over time and by age, disease syndrome, disease severity, geographical region and the presence
of antimicrobial-resistant genes.

• Of the estimated 5.83 million deaths among children < 5 years of age globally in 2015, 294 000
(uncertainty range [UR], 192 000–366 000) were estimated to be caused by pneumococcal infections.

• Before the introduction of pneumococcal conjugate vaccines (PCVs) in the different WHO regions, 6–11
serotypes accounted for ≥ 70% of all invasive pneumococcal disease (IPD). The reported mean annual
incidence of IPD in children aged < 2 years was 44.4/100 000 per year in Europe and 167/100 000 per
year in the United States of America., In comparison, the annual incidence of IPD in children < 2 years in
Africa ranged from 60/100 000 in South Africa to 797/100 000 in Mozambique.

• On average, about 75% of cases of IPD and 83% of cases of pneumococcal meningitis occur in children
aged < 2 years, but the incidence and age distribution of cases may vary by country, study method and
socio-economic status within countries.

• Case fatality rates from IPD in children can be high, ranging up to 20% for septicaemia and 50% for
meningitis in low and middle income countries (LMICs).

Summary of Key Points WHO Position Paper on Pneumococcal conjugate vaccines in infants and children under 5 years of age– February 2019
 Disease, diagnosis and treatment
• Pneumococcal infection and disease can affect various organ systems. Bloodstream invasion results in
bacteraemia that occasionally causes infection at secondary sites, such as the meninges, joints and peritoneum.
Contiguous spread from the nasopharynx can cause diseases such as otitis media or sinusitis.

• Pneumonia is often caused by aspiration of pneumococci from the nasopharynx and may also be caused by
blood-borne spread.

• Long-term neurological sequelae such as hearing loss, mental retardation, motor abnormalities and seizures
have been observed in 24.7% (interquartile range, 16.2–35.3%) of survivors of childhood pneumococcal
meningitis; the risk of sequelae was 3 times higher among survivors in Africa and Asia than among those in
Europe.

• Lack of exclusive breastfeeding, nutritional deficiency and indoor air pollution are risk factors for pneumonia,
including pneumococcal pneumonia, in infants and young children.

• While clinical diagnosis of pneumonia or meningitis is based on symptoms, signs and radiological tests,
diagnosis of pneumococcal disease requires laboratory confirmation. A definitive diagnosis of pneumococcal
infection is made by isolating the bacterium from blood or other normally sterile body sites, such as
cerebrospinal fluid.

• Pneumococcal disease can be treated with antimicrobials. The choice of antimicrobial and the duration of
treatment depend on the site of infection and the pattern of susceptibility to antimicrobials; the outcome depends
on age, disease syndrome, severity, duration of illness before initiation of treatment and susceptibility to the
antimicrobials used.

Summary of Key Points WHO Position Paper on Pneumococcal conjugate vaccines in infants and children under 5 years of age– February 2019
 Pneumococcal conjugate vaccines
• Two polysaccharide-protein conjugate vaccines have been on the market since 2009: the 10-valent (PCV10)
and the 13-valent (PCV13) vaccines. Previously, a 7-valent pneumococcal conjugate vaccine (PCV7) was
available.

• This position paper pertains to the currently licensed PCV10 and PCV13 used in children < 5 years of age.

• Both PCV10 and PCV13 have been shown to be safe and effective and to have both direct (in vaccinated
individuals) and indirect (in unvaccinated individuals living in communities with vaccinated children) effects
against pneumococcal disease caused by vaccine serotypes when used in a 3-dose schedule (either 2p+1 or
3p+0) or in a 4-dose schedule (3p+1).

• After the third dose of each schedule (post-booster for 2p+1 and post-primary for 3p+0), the 2p+1 schedule
resulted in higher GMCs but a similar percentage of responders as compared with a 3p+0 schedule for most
serotypes, except for serotype 6B, for which the percentage of responders was higher with the 2p+1 schedule.

• Both PCV10 and PCV13 induce antibodies against the serotypes common to both vaccines (1, 4, 5, 6B, 7F, 9V,
14, 18C, 19F and 23F). Although the mean antibody response to the common serotypes differed with the 2
products, in general, they induced comparable immunogenicity.

• PCV13 has 3 additional serotypes, 3, 6A and 19A. PCV13 induces an immune response to serotype 3; PCV10
contains neither serotype 3 nor any cross-reactive serotype, and immunogenicity against serotype 3 is not
measured in studies of this vaccine. Both PCV10 and PCV13 induce an antibody response to serotype 6A,
which is included in PCV13 but not in PCV10. Both PCV10 and PCV13 induce an antibody response against
serotype 19A.

Summary of Key Points WHO Position Paper on Pneumococcal conjugate vaccines in infants and children under 5 years of age– February 2019
 WHO Position
• WHO recommends the inclusion of PCVs in childhood immunization
programmes worldwide.

• Currently available PCVs are safe and effective, and the increase in the number
of serotypes in these vaccines as compared with the first licensed PCV7
represents significant progress in the fight against pneumococcal disease-related
morbidity and mortality, particularly for developing countries.

• Use of pneumococcal vaccine should be complementary to other disease

prevention and control measures, such as appropriate case management,
promotion of exclusive breastfeeding for the first 6 months of life and reducing
known risk factors such as indoor air pollution and tobacco smoke.

• Despite the lack of comprehensive data on the immunogenicity, effectiveness

and safety of all possible combinations of PCV and other routine vaccines, co-
administration for programmatic reasons appears to be acceptable.

Summary of Key Points WHO Position Paper on Pneumococcal conjugate vaccines in infants and children under 5 years of age– February 2019
 WHO Position- Schedule
• For administration of PCV to infants, WHO recommends a 3-dose schedule administered either
as 2p+1 or as 3p+0, starting as early as 6 weeks of age.
• In choosing between the 2p+1 and 3p+0 schedules, countries should consider programmatic
factors, including timeliness of vaccination and expected coverage. The 2p+1 schedule has
potential benefits over the 3p+0 schedule, when programmatically feasible, as higher antibody
levels are induced in the second year of life, which may be important in maintaining herd
immunity, although no high-quality evidence is available.
• If the 3p+0 schedule is used, a minimum interval of 4 weeks should be maintained between
doses.
• If the 2p+1 schedule is selected, an interval of ≥ 8 weeks is recommended between the 2 primary
doses, but the interval may be shortened if there is a compelling reason to do so, such as
timeliness of receipt of the second dose and/or achieving higher coverage when a 4-week
interval is used. The booster dose should be given at 9–18 months of age, according to
programmatic considerations; there is no defined minimum or maximum interval between the
primary series and the booster dose.
• Previously unvaccinated or incompletely vaccinated children who recover from IPD should be
vaccinated according to the recommended age-appropriate regimens. Interrupted schedules
should be resumed without repeating the previous dose.

Summary of Key Points WHO Position Paper on Pneumococcal conjugate vaccines in infants and children under 5 years of age– February 2019
 WHO Position- Product Choice

• Both PCV10 and PCV13 have substantial impacts against pneumonia,

vaccine-type IPD and nasopharyngeal (NP) carriage.

• There is at present insufficient evidence of a difference in the net impact

of the 2 products on overall disease burden. PCV13 may have an
additional benefit in settings where disease attributable to serotype 19A
or serotype 6C is significant.
• The choice of product to be used in a country should be based on
programmatic characteristics, vaccine supply, vaccine price, the local
and regional prevalence of vaccine serotypes and antimicrobial
resistance patterns.

Summary of Key Points WHO Position Paper on Pneumococcal conjugate vaccines in infants and children under 5 years of age– February 2019
 WHO Position- Interchangeability of Vaccines

• Once a PCV vaccination programme has been initiated,

product switching is not recommended unless there are
substantial changes in the epidemiological or programmatic
factors that determined the original choice of product, e.g. an
increasing burden of serotype 19A.
• If a series cannot be completed with the same type of
vaccine, the available PCV product should be used.
• Restarting a series is not recommended, even for the
primary series.

Summary of Key Points WHO Position Paper on Pneumococcal conjugate vaccines in infants and children under 5 years of age– February 2019
 WHO Position- Catch-up Vaccination
• Wherever possible, catch-up vaccination at the time of introduction of PCV should be used to accelerate its
impact on disease in children aged 1–5 years, particularly in settings with a high disease burden and mortality.

• If there is limited availability of vaccine or of financial resources for catch-up vaccination, the youngest children
(e.g. < 2 years of age) should be prioritized to receive catch-up doses of PCV because of their higher risk for
pneumococcal disease.

• Catch-up vaccination can be done with a single dose of vaccine for children ≥ 24 months.

• Current data are insufficient for a firm recommendation on the optimal number of doses (1 or 2) required in 12–
23-month-olds as part of catch-up vaccination, so countries choosing to use 1 dose might wish to monitor for
impact and vaccine failures.

• Unvaccinated children aged 1–5 years who are at high risk for pneumococcal infection because of underlying
medical conditions, such as HIV infection or sickle-cell disease, should receive at least 2 doses separated by at
least 8 weeks.

• In humanitarian or other emergency situations, age-appropriate schedules of PCV vaccination should be used
for children < 1 year of age and considered for children ≤ 5 years of age, as indicated by the situation.

• Catch-up vaccination may also be an important means to prevent outbreaks. Vaccine campaigns in response to
outbreaks of confirmed vaccine-type pneumococcal disease are under consideration, but experience is currently
lacking.

Summary of Key Points WHO Position Paper on Pneumococcal conjugate vaccines in infants and children under 5 years of age– February 2019
 WHO Position- Vaccination of Special Populations

• PCVs should not be given to individuals with a history of anaphylactic

reactions or severe allergic reactions to any component of the vaccine.

• HIV-positive infants and pre-term neonates who have received their 3

primary vaccine doses before 12 months of age may benefit from a
booster dose in the second year of life.
• Travelling children are generally not at special risk of pneumococcal
disease, unless they travel to an outbreak setting. They should follow the
vaccine recommendations for the general population and ensure they
are up to date with their vaccinations before travelling.

Summary of Key Points WHO Position Paper on Pneumococcal conjugate vaccines in infants and children under 5 years of age– February 2019
 WHO Position- Surveillance
• While a comprehensive surveillance system for pneumococcal disease is
recommended, countries without such a system in place should not wait to
introduce PCV vaccines.

• WHO recommends that the epidemiological impact of PCV be carefully

monitored in sustained, high-quality sentinel and population-based surveillance
for pneumococcal disease and in periodic NP carriage surveys.

• Such surveillance and surveys should be conducted to monitor changes in

disease and the circulation of pneumococcal serotypes in the community after
use of different PCV products at different dosing schedules and in different
geographical and epidemiological settings with different pneumococcal disease
burdens and transmission.

• Ideally, surveillance should be started at least 1–2 years before introduction of

PCV and be continued indefinitely but at least for 5 years after introduction.

Summary of Key Points WHO Position Paper on Pneumococcal conjugate vaccines in infants and children under 5 years of age– February 2019
 WHO Position- Research Priorities

• Additional research should be conducted on:

• further assessment of vaccine impact, duration of protection and indirect effects of
different dosing schedules;
• serotype replacement;
• further establishment of serotype-specific immune correlates of protection against IPD
in different transmission settings;
• the epidemiology of pneumococcal outbreaks, particularly epidemics of serotype 1
disease, including use of PCV to prevent or respond to outbreaks;
• the impact of PCV on antimicrobial use and resistance;
• comparison of a 1-dose versus a 2-dose catch-up schedule for children > 12 months of
age.

Summary of Key Points WHO Position Paper on Pneumococcal conjugate vaccines in infants and children under 5 years of age– February 2019