Pneumococcal

Streptococcus pneumoniae (pneumococcus), a gram-positive bacteria of which there are some 90 identifiable serotypes; of these, 23 are responsible for an estimated 90% of cases of invasive pneumococcal disease. However some types more commonly affect children, while others are of greater significance in adults.

Pneumococci are common inhabitants of the respiratory track and can be isolated from the nasopharynx in 5–70% of normal adults.

The risk of disease is higher in infants and elderly, and those with predisposing conditions such as chronic respiratory conditions, diabetes, congestive heart failure, renal failure, CSF leaks, or immune deficiency states, including asplenia, sickle cell anaemia, HIV infection, post-organ transplant and Hodgkins disease.

Signs Symptoms and Complications

Pneumococcal infection is the most common bacterial cause of otitis media in children, and a frequent cause of sinusitis and pneumonia in all age groups. Invasive pneumococcal diseases cause bacteraemia and meningitis, especially in the very young. It can also occasionally cause endocarditis and very rarely affect other sites in the body such as joints, the peritoneal cavity.

Pneumococcal pneumonia is the most common clinical presentation with an incubation period of 1-3 days and clinical features of:

• Abrupt onset of fever with shaking chills and rigors
• Pleuritic chest pain
• Productive cough (mucopurulent, rusty sputum)
• Dyspneoa (shortness of breath), Tachypnoea (rapid breathing)
• Tachycardia (rapid heart rate) and hypoxia (poor oxygenation) may be present in severe disease

Pneumococcal meningitis is a common manifestation of pneumococcal disease worldwide. Clinical features include:

• Neck stiffness
• Photophobia
• Nausea
• Vomiting
• Seizures or coma
• Confusion
• Focal neurological deficits may develop in advanced disease.

Mortality rates are around 30% but as much as 70% in the elderly, and neurological sequelae are common in survivors.

Pneumococcal bacteraemia is a common cause of septicaemia in infants under 2 years worldwide and accounts for approximately 70% of invasive disease in this age group. Bacteraemia commonly accompanies pneumococcal meningitis and pneumococcal pneumonia and includes clinical features of:

• Fever with chills and rigors
• Dyspnoea
• Tachypnoea
• Hypoxia and mixed respiratory and metabolic acidosis
• Pallor
• Confusion

Patients should be referred for a specialist medical assessment to screen for osteomyelitis, renal failure and myocarditis.

Otitis media presents in children and infants with:

• Pain
• Irritability
• Fever
• Conductive hearing loss
• Erythema, fluid levels and/ or suppuration may be seen on otoscopy

Sinusitis may present with:

• Nasal discharge
• Periorbital, frontal or dental pain
• Cough, due to post-nasal drip
• Pain, photophobia, periorbital oedema, reduced visual acuity and reduced eye movements if the disease spreads into the adjacent orbit.
  

Method of Transmission

• Airborne droplet
• Person to person direct contact

Public Health Significance

The WHO estimates that pneumococcal disease causes over one million deaths per year, mostly in children under five years of age, in countries with developing economies. In countries with developed economies, it causes an estimated 100 cases of pneumonia, 15-19 cases of febrile bacteraemia and 1-2 cases of meningitis per 100,000 people each year, with the pneumococcal pneumonia death rate averaging 10-20% and exceeding 50% in high risk groups (the elderly, transplant patients, those who are immunosuppressed, patients with chronic cardiac, respiratory or renal disease, alcoholism, type 1 or 2 diabetes or current viral upper respiratory tract infection).

The incidence of resistance of Streptococcus pneumoniae to antibiotics (up to 15% of strains are penicillin resistant in some areas) means that vaccination is assuming greater importance.

Otitis media causes significant morbidity in the paediatric population; complications may lead to hearing loss, and behavioral and learning difficulties.

Pneumococcal disease occurs year round however is more common during autumn and winter.

New Zealand Epidemiology

Pneumonia is an important illness in the first year of life, with high rates for children up to five years of age. After this the incidence declines over the first decade of life and remains at low levels until the age of 50, then starts rising steeply from 65 years of age. Only 18 percent of hospitalisations with pneumonia in 1995 had a cause identified, with pneumococcal pneumonia the most commonly coded organism in 8 percent of hospitalisations. This may underestimate the proportion of cases of pneumonia caused by S. pneumoniae as the organism is not identified in all cases, and not all are coded accurately where the organism is found.

A population based Auckland review of invasive pneumococcal disease (IPD) in children from 1984 to 1992 found:

• An average annual incidence of 22 per 100,000 for children under 15 years
• 56 per 100,000 in children under five years and
• 110 per 100,000 in children under two years. 
• The rates were higher in Maori and Pacific children.
• The rates of invasive disease for Maori and Pacific children under 15 years were 28 per 100,000 and 49 per 100,000.
• The rate was especially high in Pacific children under two years of age with a rate of 215 per 100,000.
• Rates of pneumococcal meningitis in all children under the age of two years was 23 per 100,000, and was 46 per 100,000 in Pacific children.
• Further data from Auckland prospective surveillance during 2000/01 found the rate of invasive disease in all children under the age of two years was 191 per 100,000.
• For Maori children the rate was 217 per 100,000 and for Pacific 296 per 100,000.
• The rate of pneumococcal meningitis in children under the age of two years in Auckland remains high with a rate of 30 per 100,000 in all children, and rates of 43 per 100,000 and 49 per 100,000 in Maori and Pacific children.
• Lower rates for all New Zealand of 80 per 100,000 are likely to reflect less than complete referral of isolates in a passive surveillance system, and different rates of disease through the country.
• More recent information comes from isolates from invasive disease, which are serogrouped and serotyped at the Institute of Environmental Science and Research (ESR) reference laboratory. The most common serogroups/serotypes in 2003/04 were 14, 9, 19, 4 and 23F.

Summarised from the 2006 New Zealand Immunisation Handbook [Click Here for PDF of Pneumococcal Chapter]

A report for IMAC of the New Zealand Burden of Pneumococcal Disease  click here

Non Immunisation Related Preventions

The spread of the organism within a family or household is influenced by such factors as:

• Overcrowding
• The presence of other upper respiratory infections
• Season (all year, but more common in autumn and winter months)
• Good hygiene practices (covering coughs and sneezes), hand washing and avoidance of overcrowded spaces may help.

Vaccines and Vaccination

There are two types of vaccine available against Streptococcus pneumoniae:

• A 23-valent polysaccharide vaccine (23PPV) is used in children over two years of age and adults. Like other polysaccharide antigens children under 2 years of age do not mount an effective immune response following vaccination. The vaccine contains the polysaccharide capsules of the 23 pneumococcus serotypes that cause 90% of invasive disease in countries with developed economies. This is dissolved in normal saline and 0.25% phenol.
• Newer protein conjugate vaccines (PCV7) are licensed in some countries including New Zealand for use in infancy and childhood. These contain polysaccharide capsules from seven serotypes coupled to an immunogenic carrier protein from Corynebacterim diphtheriae and adsorbed onto an aluminium adjuvant. It is important to note that this vaccine does not confer immunity to diphtheria. PCV7 is the pneumococcal vaccine offered to children born from 01 January 2008 on the National Childhood Immunisation Schedule.

Efficacy and Effectiveness

23PPV (23-valent pneumococcal polysaccharide vaccine)

• More than 80% of healthy adults produce an antibody response within 2-3 weeks of vaccination. 
• Overall estimated effectiveness in preventing invasive disease is 60-70% for the vaccine serotypes. 
• Older adults, and persons with some chronic illnesses or immunodeficiencies may not respond as well, if at all. However as mortality in these groups, particularly those with chronic illness is so high vaccination is still recommended.
• The efficacy against non-bacteraemic pneumonia is unclear.
• The vaccine does not appear to affect carriage rate.
• Immunity wanes relatively rapidly.
  

PCV7 (7-valent pneumococcal conjugate vaccine)

• For the active immunisation of infants and children aged 6 weeks to 10 years.
• After 4 doses of PCV7 virtually all healthy infants develop antibodies to all 7 serotypes.
• Large clinical trial demonstrated 97% reduction in invasive disease caused by the 7 serotypes.
• Efficacy against pneumonia varied depending on the specificity of the diagnosis. 
• Clinically diagnosed pneumonia shows reduction by 11%, but pneumonia confirmed by X-ray with consolidation of greater than or equal to 2.5cm showed reduction by 73%.
• Children who received 7vPCV had 7% fewer episodes of acute otitis media and underwent 20% fewer typanostomy tube placements.
• The duration of protection is currently unknown.

Availability

There are two different pneumococcal vaccines available in New Zealand:

• For Infants and Children: Prevenar^® (7-valent pneumococcal conjugate vaccine)
• For Older Children and Adults: Pneumovax^®23 (23-valent pneumococcal polysaccharide vaccine)

It is important to understand the differences between the three vaccines:

• Prevenar^® is a conjugate vaccine. It is constructed and functions in a similar way to the Haemophilus influenzae type b (Hib) vaccine. The pneumococcal polysaccharide is linked to an immunogenic protein. It converts a T-cell independent response to a T-cell dependent response. The T-cell involvement allows Prevenar^® to induce an effective immune response in children under 2 years of age. Prevenar^® covers the 7 strains of pneumococcal bacteria that caused 88% of invasive disease in New Zealand children under five in 2002. Prevenar^® is licensed for children 6 weeks to 9 years of age.
• Pneumovax^®23 is a polysaccharide vaccine. Polysaccharide vaccines induce a T-cell independent response and infants under 2 years old do not develop a protective immune response to this vaccine. Hence, it is not recommended for infants under 2 years old. Pneumovax^®23 contains the 23 serotypes which cause 90% of invasive disease in industrialized countries. Response to vaccination is often diminished in immune compromised individuals although they are at higher risk of pneumococcal disease and are a priority group for immunisation.

Eligible Groups for the Nationally Funded Programme:

• Some children under 5 years old with medical conditions that place them at very high risk of invasive pneumococcal disease are eligible to receive both Prevenar^® and Pneumovax^®23 FREE OF CHARGE (upon secondary care specialist recommendation) as part of the pneumococcal At-risk  programme. Refer below for details of which medical conditions are funded.
• Individuals of any age pre or post splenectomy, and children aged 0 to 16 years with functional asplenia, are eligible for Prevenar^® and/or Pneumovax^®23 FREE OF CHARGE (upon secondary care specialist recommendation). See the attached Pneumococcal Quick Flip for more detail.

Pnuemococcal Immunisation Recommended – But NOT Funded

• 1. All individuals with medical conditions that place them at higher risk of pneumococcal disease. Refer below for more details.
• 2. All “healthy” children under the age of 5 years are recommended Prevenar^®, particularly Maori, Pacific Island and children attending day care centres.

Prevenar^® is available to all other infants and children through the private market and is licensed for children 6 weeks to 9 years of age. NB: Prevenar^® is now funded in the immunisation programmes of the USA, Australia, the Netherlands, Greece, Qatar, Mexico, Canada and the UK. 

Pneumovax^®23 is funded in most developed countries including USA, Australia, and the UK and in most countries of the EU.

Ordering:
Nationally Funded Programme: from ProPharma stores. Refer to the Immunisation Handbook 2006, pages 38 & 39 and Chapter 16, for details on eligibility and administration.

Private Market:
Prevenar^® via Wyeth
Phone: 0800 734 076, press 4, fax 0800 Wyeth.

Pneumovax^®23 via MSD.
Phone: 0800 800 673, fax:0800 808 673 or www.msdvaccines.co.nz

Very high risk (funded programme) and high risk (not funded)

Age at Start	Recommended pneumococcal immunisation course
6 weeks to 6 months old	4 doses PCV7 given with routine immunisations at 6 weeks, 3, 5 and 15 months OR Doses 1 , 2 and 3 at least 6-8 weeks apart and dose 4 at 15 months Followed by: 2 doses of 23PPV given at 2 years and 4-5 years of age
7 - 11 months	3 doses of PCV7 given. Dose 1 and 2 at least 6-8 weeks apart and dose 3 at 15 months Followed by: 2 doses of 23PPV given at 2 years and 4-5 years of age
12 - 59 months	2 doses of PCV7 given at least 6-8 weeks apart Followed by: 2 doses of 23PPV given 3-5 years apart (Ideally at 2 years and 4-5 years)
5 - 9 years	1 dose of PCV7 Followed 6 - 8 weeks later by: 1 dose of 23 PPV
10 - 16 years1	1 dose of 23PPV
16 years and older2	1 dose of 23PPV
	Booster dose of 23PPV 5 yearly - for asplenic patients only

Footnotes:

1. Some paediatricians may recommend one dose of PCV7 and one dose of 23PPV

2. For HIV infected people some specialists may recommend one dose of PCV7 and one dose of 23PPV.

Additional at-risk population groups - Recommended BUT NOT FUNDED

Age at start of course	Recommended pneumococcal immunisation course
6 weeks to 6 months old	4 doses PCV7 given with routine immunisations at 6 weeks, 3, 5 and 15 months OR Doses 1 , 2 and 3 at least 6-8 weeks apart and dose 4 at 12 - 15 months
7 - 11 months	3 doses of PCV7. Dose 1 and 2 at least 6-8 weeks apart and dose 3 at 12 - 15 months
12 - 23 months	2 doses of PCV7. Dose 1 and 2 given 6 - 8 weeks apart
24 - 59 months	1 dose of 23PPV
Adults over 65 years	1 dose of 23PPV

For a printable version of this chart on Recommended Pneumococcal Immunisation Doses and At-Risk Groups Click Here

Dosage and Administration

23-valent pneumococcal polysaccharide vaccine (23PPV)

• The dose is 0.5 mL as a single dose, by either SC or IM injection for individuals over 2 years of age.  Boosters may be required for some individuals (see Indications and Recommendations below).

7-valent pneumococcal conjugate vaccine (PCV7)

• The dose is 0.5 mL by IM injection.
• For infants this is usually given as a 3-dose primary course at 8-12 weekly intervals beginning at approximately 2 months. A fourth (booster) dose is recommended at 12 – 15 months of age.
• If starting at 7 – 12 months of age a primary course consists of two doses at least 4 weeks apart, followed by a booster dose at 12 – 15 months.
• If starting age 12 months to 23 months, only 2 doses are required at least 8 weeks apart.
• Healthy children over 2 years of age require only a single dose, but children with chronic illness such as asplenia, sickle cell disease, HIV infection, chronic illness or immunocompromising conditions should receive 2 doses at least 8 weeks apart.
• PCV7 should be administered in a separate syringe.

Indications and Recommendations

Very High Risk Individuals (Funded)

• All ages pre or post splenectomy
• Children (0–16 years) with functional asplenia
• Children under 5 years of age with the following high-risk conditions
  • On immunosuppressive therapy or radiation therapy
  • Primary immune deficiencies
  • HIV
  • Renal failure or nephrotic syndrome
  • Organ transplants
  • Cochlear implants or intracranial shunts
  • Chronic CSF leaks
  • On corticosteroid therapy for more than 2 weeks, at daily prednisone dose of  ≥2 mg/kg or a total dose ≥ 20mg
  • Pre-term infants, born at under 28 weeks gestation
  • Chronic pulmonary disease (including asthma treated with high dose corticosteroid therapy)
  • Cardiac disease with cyanosis or failure
  • Insulin dependent diabetes
  • Down's syndrome

High Risk Individuals (Not Funded)

• All ages over 5 years with the following very high risk conditions:
  • on immunosuppressive therapy, primary immune deficiencies, HIV, renal failure or nephritic syndrome, organ transplants, cochlear implants or intracranial shunts, chronic CSF leaks, on long term corticosteroid therapy.
• Children under 5 with other high risk conditions:
  • Pre-term infants born under 28 weeks gestation, Pre-term infants with chronic lung disease discharged home on oxygen, cardiac disease with cyanosis or failure, Bronchiectasis, insulin dependent diabetes, Down Syndrome.
• Children over 5 and adults with other risk conditions:
  • Other Immune compromised conditions e.g. myeloma, Hodgkin’s disease, chronic illness eg diabetes, alcoholism, cardiac, renal or pulmonary disease, Down Syndrome, previous pneumococcal invasive disease.

Additional at-risk population groups (Not Funded)

• All healthy children under 5 years old (Particularly Maori and Pacific children and all children attending early childhood services.)
• All adults 65 years and over

Adverse Reactions

23-valent pneumococcal polysaccharide vaccine

• About half the recipients of 23vPPV will experience some soreness after the first dose, but pain or swelling severe enough to limit arm movement occurs in less than 5% of recipients.
• Low-grade fever occurs occasionally, but fever above 39°C occurs in less than 0.5% of recipients.
• First revaccination is associated with an increase in local adverse events, with about three-quarters of vaccinees experiencing soreness at the injection site, and ≥10% of recipients experiencing a moderate or greater limitation -albeit temporary- of arm movement.
• Revaccination is not associated with an increase in systemic adverse events such as fever or headache.

7-valent pneumococcal conjugate vaccine

• Commonly reported adverse events are injection site reactions and fever, with rates of erythema ranging from 10.0 to 11.6%.
• There is no increased local reactogenicity with subsequent doses
• A higher rate of local reactions occurs in older children after a single dose.
  

Contraindications

23-valent pneumococcal polysaccharide vaccine

• The only absolute contraindications to 23vPPV are anaphylaxis after a previous dose of the vaccine or anaphylactic sensitivity to any vaccine components.
• Immunisation is not recommended in children under 2 years unless they have completed the relevant course of 7vPCV.
  

7-valent pneumococcal conjugate vaccine

• Anaphylactic sensitivity to either a previous dose or to any components of the vaccine.

Use in pregnancy

• 23-valent pneumococcal polysaccharide vaccine -Although 23vPPV has been administered in pregnancy with no evidence of adverse effects, trial data is limited. Only women at high risk of Invasive Pneumococcal Disease should be vaccinated.
• 7-valent pneumococcal conjugate vaccine - Studies of safety and efficacy in pregnancy are too limited for vaccination to be recommended.
  

Risks of disease vs risks from vaccine 

Disease	Effect of disease	Side effects from vaccine
Pneumococcal infections - bacteria spread by droplets, causing fever, pneumonia, septicaemia, meningitis and otitis media.	Mortality rate for pneumococcal pneumonia in countries with developed economies is 10-20%. Case fatality for IPD can be as high as 50% in high risk patients.	Polysaccharide vaccine - local reactions common -also mild fever, headache, malaise  (1 in 30). Conjugate vaccine - about 1 in 10 have local reaction or fever.