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Chapter 16 Pneumococcal Infection
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Pneumococcal Infection
PPV introduced for “at risk” 1996
PCV7 introduced for “at risk” 2002 and as routine 2008
PCV13 replaced PCV7 in 2010
NOTIFIABLE
In some circumstances, advice in these guidelines may differ from that
in the Summary of Product Characteristics of the vaccines. When this
occurs, the recommendations in these guidelines, which are based on
current expert advice from NIAC, should be followed.
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Introduction
Streptococcus pneumoniae (pneumococcus) is an important cause
of serious infection, especially in young children, older adults and
immunocompromised people. Invasive pneumococcal disease (IPD) is
defined as the isolation of S. pneumoniae from a normally sterile site (e.g.
blood, cerebrospinal fluid (CSF), joint, pleural, or pericardial fluid).
IPD is a disease mainly occurring in children under 5 years and those aged
≥65 years. Individuals with severe chronic disease or immunodeficiency are
also at increased risk of this disease. Non-invasive manifestations of the
disease include otitis media, particularly in children, sinusitis and bronchitis.
Although more than 90 polysaccharide capsular serotypes of pneumococci
are known, most infections are caused by a limited number of serotypes. In
Europe in 2010, the serotypes most commonly implicated were 1, 3, 4, 7F, 8,
12F, 14, 19A, 19F and 22F. The fact that relatively few serotypes cause most
invasive disease has allowed for the development of effective vaccines.
Epidemiology
Pneumococcal infection is a leading cause of death worldwide. Mortality
is highest in patients who develop sepsis or meningitis. Pneumococcal
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meningitis case fatality rates of 11-16% were reported in Ireland in the years
2004-2010 and in 2011, a case fatality rate of 9% was reported associated
with IPD. Transmission is from person to person by droplet infection or direct
contact with respiratory secretions of someone carrying the organism. The
incubation period varies by site of infection, and can be as short as 1-3 days.
Infection can occur at any time throughout the year but rates peak during the
winter months (Figure 16.1).
Figure 16.1 Invasive pneumococcal disease (IPD) notifications in Ireland by
month, 2007–2012
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Source: HPSC
Each year the age specific incidence rates (ASIR) are highest among the
elderly and young children. A decline in ASIR in the youngest age groups is
evident in recent years (Figure 16.2).
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Figure 16.2 Age-specific incidence rates of confirmed invasive pneumococcal
disease (IPD) notifications, 2008-2012
Source: HPSC
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In Ireland PCV7* was recommended for at risk children in 2002 and was
introduced into the routine primary immunisation schedule in September
2008, along with a catch up programme for all children under 2 years of age.
In December 2010 PCV13** vaccine replaced PCV7 in the Irish childhood
immunisation programme. PCV13 includes antigens from the seven serotypes
contained in PCV7 plus six additional serotypes which cause IPD.
Since the introduction of PCV7 there has been a 91% decrease in the
incidence of IPD in young children due to PCV7 serotypes. The additional
impact of the introduction of PCV13 should become evident over the next few
years.
Pneumococcal conjugate vaccines reduce the rates of nasopharyngeal
colonisation by vaccine serotypes, thus decreasing the potential for
transmission from vaccinated to unvaccinated persons. In the US there has
been a significant reduction in the incidence of IPD in the adult population
since 2001, following the introduction of PCV to their childhood vaccine
schedule.
*PCV 7
4, 6B, 9V, 14, 18C, 19F, 23F
**PCV 13 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19 A, 19F, 23F
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In Ireland, since 2008, based on notification data the burden of confirmed
cases of IPD in the total population has been reduced by 9%. The greatest
reduction have been seen in young children, particularly in those <2 years of
age (Figure 16.2). Based on data available from the National Pneumococcal
Typing Laboratory, the decrease in this age group can largely be attributed
to a significant decline (>76%) in IPD due to serotypes covered by PCV7
between Jan-June 2008 and 2012 (Figure 16.3).
Although overall incidence of IPD has decreased compared with 2008, some
increase in the burden of illness due to non-PCV7 serotypes has emerged.
The impact of the PCV7 vaccine on notifications is evident in the number of
confirmed IPD cases in those <2 years of age decreasing from 51 reported in
2008 to 16 cases in 2012. A decline in notifications of disease caused by the
additional serotypes included in the PCV13 was not yet evident in 2012. Any
change in non-PCV 13 serotypes over time needs to be closely monitored.
Figure 16.3 Number of IPD cases in all ages due to serotypes covered by
PCV7, PCV13 and non PCV13, 2008-2012.
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Source: HPSC, from National Pneumococcal Typing Laboratory
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Effects of pneumococcal infection
Pneumococcal infection is the most common cause of bacteraemia,
septicaemia, bacterial meningitis, pneumonia, sinusitis, and acute otitis
media in children. It can also cause periorbital cellulitis, endocarditis,
pericarditis, peritonitis, and soft tissue, bone and joint infection.
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Clinical Risk Groups
Persons with the following medical conditions are at risk of pneumococcal
infection:
• chronic respiratory disease including
m a
sthma which requires continuous or frequently repeated use of
oral steroids
m b
ronchiectasis
m b
ronchopulmonary dysplasia (BPD)
m c hronic obstructive pulmonary disease (COPD)
m c ystic fibrosis
m i nterstitial lung fibrosis
m p
neumoconiosis
m r espiratory conditions caused by aspiration
• hyposplenia or asplenia (including those with sickle cell and coeliac
disease)
• immunocompromised by disease or its treatment
• neuromuscular disease (e.g. cerebral palsy) with a risk of aspiration
In addition smoking, alcohol abuse and exposure to metal fumes also
increase the risk of pneumococcal infection.
Cigarette smokers are at significantly increased risk of invasive pneumococcal
disease. In a US study, the risk for IPD among immunocompetent cigarette
smokers aged 18-64 years was four times the risk for controls who had never
smoked. Significant dose-response relationships with risk for IPD were also
observed for number of cigarettes smoked and pack-years of smoking.
Smoking also increases the risk for IPD among other groups, including
immunocompromised persons.
Individuals with a history of alcohol abuse are 1.6- 7.1 times more likely to
develop IPD than the general population. Proposed reasons for the higher
risk include increased bacterial colonisation, reduced ciliary motility and
immune system compromise.
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There is an association between exposure to metal fumes (e.g. welding) and
pneumonia and between welding and invasive pneumococcal disease.
Management of cases, contacts, and outbreaks
Cases of invasive pneumococcal disease (IPD)
Any case of invasive pneumococcal infection or lobar pneumonia believed to
be due to S. pneumoniae should prompt a review of the patient’s history to
establish whether they are in a risk group and have been vaccinated. Patients
with risk factors who have not previously been vaccinated should be given
pneumococcal vaccination on discharge from hospital; they should continue
vaccination as for other at-risk people (see section on recommendations for
the use of pneumococcal vaccination).
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Contacts of cases
Antibiotic prophylaxis is not indicated for close contacts of a case of invasive
pneumococcal disease as such contacts are not normally at increased risk of
pneumococcal infection. Clusters of invasive pneumococcal disease should
be discussed with local Specialists in Public Health Medicine.
Outbreaks
Outbreaks of pneumococcal infection in hospitals and residential care homes
need prompt investigation. Control measures, including vaccination, may
be appropriate; these measures should be agreed in discussion with local
health-protection or infection-control teams.
Pneumococcal vaccines
There are two types of pneumococcal vaccine.
• Pneumococcal polysaccharide vaccine (PPV23) contains purified capsular
polysaccharide from 23 capsular types* of pneumococcus which account
for up to 90% of IPD. It is only indicated for those ≥2 years of age; as an
adequate antibody response does not develop in those under 2 years of
age.
• Pneumococcal conjugate vaccine contains polysaccharide antigens from
10 (PCV 10) or 13 (PCV 13) serotypes* conjugated to a protein. (PCV7 is no
longer available). These have enhanced immunogenicity to their constituent
* The following serotypes are contained in pneumococcal vaccines
PCV 7
4, 6B, 9V, 14, 18C, 19F, 23F
PCV10 1, 4, 5, 6B, 7F, 9V, 14 18C, 19F, 23F
PCV 131, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F
PPV23 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F
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antigens compared with the polysaccharide vaccine, and are immunogenic
from 6 weeks of age. Conjugate vaccines are active against 75-90% of
serotypes causing IPD, including a significant number of penicillin-resistant
strains. The number of doses required for optimum immunogenicity
depends on the age and immune status of the recipient. There is a lower
response to conjugate vaccines in preterm infants, but the response is
adequate to confer significant protection.
An up to-date list of licensed vaccines can be accessed on the HPRA website
www.hpra.ie
A list of the vaccines currently available from the National Cold Chain Service
and be found at www.immunisation.ie
Pneumococcal vaccines should be stored at +2 to +8oC.
Dose and route of administration
1. Pneumococcal Conjugate Vaccine (PCV). The dose is 0.5 ml given by
intramuscular injection in the deltoid or the anterolateral thigh.
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2. Pneumococcal Polysaccharide Vaccine (PPV23). The dose is 0.5 ml given
by intramuscular injection in the deltoid.
Indications for pneumococcal vaccination.
1. Routine Childhood Pneumococcal Conjugate Vaccine (PCV)
The course consists of 3 doses at 2, 6 and 12 months of age.
Older children aged 12- <24 months of age who have not received PCV
vaccine require 1 dose.
For children aged 12-< 24 months, PCV and seasonal influenza vaccine
administration should be separated by an interval of at least one week (to
decrease the risk of febrile convulsions occurring).
PCV is not recommended for children aged over 24 months unless they are
in an at risk group (see below).
2. Routine Adult Pneumococcal Polysaccharide Vaccine (PPV23)
One dose of PPV23 is recommended for all aged 65 years and older.
3. Clinical Risk Groups
The following groups are considered at higher risk of invasive
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pneumococcal disease than the general population and often both PCV
and PPV23 are recommended (see Table 16.1).
Table 16.1 Clinical risk groups who require pneumococcal vaccination
Group A
Those at high risk
Group B
Children at medium
risk
Group C
Adults at medium
risk
• Asplenia, hyposplenia (including
splenectomy, sickle cell disease,
haemoglobinopathies, and
coeliac disease) 1
• Chronic renal
disease or nephrotic
syndrome
• Chronic renal
disease or nephrotic
syndrome
• Chronic heart, lung,
or liver disease
• Chronic heart,
lung, or liver
disease
• Complement deficiency
(particularly C1-C4)
• Immunosuppressive conditions
(e.g. some B- and T-cell disorders,
HIV infection, leukaemia,
lymphoma,) and those receiving
immunosuppressive therapies2
• CSF leaks (congenital or
complicating skull fracture or
neurosurgery)
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• Intracranial shunt
• Diabetes mellitus
requiring insulin or
oral hypoglycaemic
drugs
• Down syndrome
• Children under
5 years of age
following invasive
pneumococcal
disease
• Candidates for, or recipients of, a
cochlear implant
• Diabetes mellitus
requiring insulin or
oral hypoglycaemic
drugs
• Smokers and
alcoholics
• Individuals with
occupational
exposure to metal
fumes (i.e. welders)
• Post haematopoietic stem-cell
transplant
• Solid organ transplant
1
2
require 2 doses of PCV 2 months apart
individuals with primary immunodeficiency may have a suboptimal response to all vaccines.
Pneumococcal vaccines are unlikely to be immunogenic in children with primary immune
deficiencies involving significant B cell compromise who are receiving regular IVIG replacement
therapy. However vaccination should be given as it may have some effect.
3.1 C
hildren
2 -<5 years
Risk group A: PCV and PPV23
Risk group B: PCV and PPV23
5 - <18 years
Risk group A: PCV and PPV23
Risk group B: PPV23
3.2 Adults
Risk group A: PCV and PPV23
Risk group C: PPV23
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For vaccine types and schedule see Table 16.2 below.
Pneumococcal vaccination should ideally be completed at least 2 weeks
prior to elective splenectomy or cochlear implant.
Table 16.2 Pneumococcal immunisation for children and adults at increased
risk of IPD
Age at first
vaccination
Vaccine type, number of doses and intervals
PCV
6 weeks -<12 months
Doses 1 & 2 at 2 month
intervals
Dose 3 at ≥12 months of age,
≥ 2 months after dose 2
PPV23
1 dose given ≥24
months of age,
( ≥2 months after final
dose of PCV)
1 or 2 doses1 at 2 month
intervals
24 months to 5 years2
1 or 2 doses1 at 2 month
intervals
1 dose
(≥2 months after
PCV)
>5- <18 years2
0, 1 or 2 doses1 2
18 and older
0, 1 or 2 doses1 2
1 dose
( ≥2 months after PCV
if given)
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12-<24 months
1 dose of PCV required for all medically at risk over 12 months except when response may be
blunted e.g. asplenia/hyposplenia including sickle cell disease, IgA-, IgG subclass- and specific
antibody deficiencies. This group needs 2 doses unless they have previously received PCV or
PPV23 in which case they need 1 dose of PCV.
1 2
1 dose of PCV13 may be given to at-risk children who have completed a course of PCV7.
For those who have received PPV23, wait ≥ 1 year before giving PCV to
optimise the immune response.
4. Cases of invasive pneumococcal disease (IPD)
Patients with risk factors who have not been vaccinated should be given
pneumococcal vaccination before discharge from hospital; they should
continue vaccination as for other at-risk people.
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Following IPD in a child under 5 years of age, full blood count,
immunoglobulin levels (including IgG sub classes) and complement levels
should be checked.
All children under 5 years of age who have had IPD, even if not in a clinical
risk group, should receive a dose of PCV irrespective of vaccine history
followed by a dose of PPV23 2 months later (at or after 2 years of age).
Children under 12 months who are unvaccinated or partially vaccinated
should complete the routine immunisation schedule followed by an
additional dose of PCV 2 months after their 12 month dose and a dose of
PPV23 at 2 years of age.
Booster doses of PPV23 (see Figure 16.4)
Booster doses are not recommended for immunocompetent people aged <65
years because of lack of evidence of improved immunity and evidence of an
increased incidence of local side-effects after repeated doses.
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For individuals whose antibody levels are likely to decline more rapidly, (e.g.
asplenia, hyposplenism, and immunosuppression) one booster should be
given 5 years after the first dose.
Adults 65 years or older should receive a dose of PPV23 if they received
PPV23 more than 5 years previously and were less than 65 years of age at
the time.
Those who received one dose of PPV23 at age 65 or older do not require any
further dose regardless of immune status.
Contraindications (PCV and PPV23)
Anaphylaxis to any of the vaccine constituents.
Precautions (PCV and PPV23)
Acute severe febrile illness; defer until recovery.
PPV23 only. Revaccination within 5 years of a previous dose of PPV23.
However, if the vaccine has been given during chemotherapy or radiotherapy,
revaccination 3 months after treatment is recommended.
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Pregnancy and breast feeding PPV23 can be given to pregnant women in
Group A Table16.1. PCV should be deferred until after delivery as, although
is unlikely to result in adverse effects, it has not been evaluated during
pregnancy.
Adverse reactions
PCV
Local: Localised tenderness and erythema at the injection site may occur.
General: Fever, irritability, decreased appetite, and increased and/or
decreased sleep.
PPV23
Local: Localised tenderness and erythema at the injection site may occur.
Reimmunisation with PPV23 can produce severe local reactions especially if
less than 5 years has elapsed since the first injection.
General: Occasional low-grade fever lasting less than 24 hours.
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* Asplenia or splenic dysfunction (splenectomy, sickle cell disease, haemoglobinopathies, coeliac syndrome); chronic renal, heart, lung, liver disease, diabetes mellitus, complement deficiency,
immunosuppressive conditions; CSF leak, cochlear implant recipients or candidates for implants; post allogeneic bone marrow transplant, solid organ transplant; children < 5 years with
history of invasive disease; smokers; alcoholics; individuals with occupational risk due to exposure to metal fumes e.g. welders.
^ Revaccination not indicated for any person who has received a dose of PPV23 at age ≥65 years.
‡ If vaccination has been given during chemotherapy or radiotherapy revaccination 3 months after treatment is indicated.
** Those with asplenia, hyposplenism, immunosuppression including HIV infection, nephrotic syndrome, renal transplant or chronic renal disease.
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Chapter 16 Pneumococcal Infection
Figure 16.4 Pneumococcal polysaccharide vaccination algorithm
Adapted from NIO
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Bibliography
American Academy of Pediatrics (2012). Red Book: Report of the Committee
on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of
Pediatrics.
Centers for Disease Control (2011). Epidemiology and prevention of VaccinePreventable Diseases. Atkinson W, Wolfe S, Hamborsky J, eds. 12th ed.
Washington DC: Public Health Foundation.
Department of Health, UK (2013) Immunisation against Infectious Diseases
(The Green Book) www.dh.gov/uk/greenbook
Health Protection Surveillance Centre (2013). Invasive pneumococcal
disease publications http://www.hpsc.ie/hpsc/A-Z/VaccinePreventable/
PneumococcalDisease/Publications/
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