Pneumococcal disease

Government advisers meet this month to consider whether or not to discontinue pneumococcus vaccination for the over-65s – largely as a result of the success of the childhood pneumococcal vaccine programme. But if this ‘herd immunity’ effect is to continue to protect older people, it is vital that uptake in children is maintained – especially in view of the serious nature of pneumococcal disease in children

Pneumococcal infections are caused by Streptococcus pneumoniae, of which there are over 90 recognised serotypes. Infection ranges from mild to life threatening, with some serotypes more likely to be associated with severe disease. The very young and the very old are particularly at risk, as are immunocompromised people (Box 1). Pneumococcal infections are most common in children under 24 months, although the incidence of invasive disease has fallen since the introduction of the pneumococcal conjugate vaccine in children.

This article discusses pneumococcal disease, how it spreads and presents, and the current preventative measures we have.

WHAT IS THE PNEUMOCOCCUS?

Pneumococci are gram-positive diplococci. They are transmitted person to person via respiratory droplet contact. They may then simply colonise the nasopharynx harmlessly, or may cause disease either by direct spread from colonised mucosal surfaces (e.g., otitis media) or by haematogenous spread. Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F cause most invasive disease, and pneumococci with these serotypes are often resistant to penicillin.

Well over a million people die each year globally due to pneumococcal diseases, mainly in developing countries and about half of these deaths occur in young children. The World Health Organization ranks pneumococcal disease as the world’s number one vaccine-preventable cause of death among children under 5 years.¹

CARRIAGE OF PNEUMOCOCCAL DISEASE

Pneumococcal colonisation of the upper respiratory tract is common and occurs in up to 60% of healthy children. Most are asymptomatic. Highest carriage rates are seen in children in daycare facilities (this is also true of other paediatric infectious diseases).² This means that pneumococci are constantly circulating in the community. There is evidence that young children continuously eradicate one serotype and then acquire another. Vaccination has changed the most commonly carried serotypes, with vaccine-sensitive serotypes becoming less prevalent.

In some individuals, for reasons that are not well understood, nasopharyngeal carriage can progress to disease, although it is harmlessly eradicated by most people who acquire it.

FORMS OF PNEUMOCOCCAL DISEASE

Pneumococcal infections are classified as non-invasive or invasive. Non-invasive disease can progress to invasive disease. Asymptomatic carriage can progress to either. Incubation period is probably one to three days.

Non-invasive pneumococcal disease

This is active pneumococcal infection that does not involve major organs or the blood. The bacterium spreads from the nasopharynx to the upper and lower respiratory tract to cause:

• Otitis media. Pneumococci are present in the middle ear in about 40% of cases of otitis media. About a third of children have at least one episode of pneumococcal otitis media by the age of 3 years. Complications may include mastoiditis and meningitis, although these are rare in otherwise healthy children.
• Non-bacteraemic pneumonia Infection of the lower respiratory tract with pneumococcus without detectable organisms in the bloodstream.

Whilst these are serious conditions with significant morbidity, death resulting from complications non-invasive disease is rare in otherwise healthy children.

Invasive pneumococcal disease (IPD)

IPD occurs when there is live bacterial multiplication inside a major organ, or in the blood. Invasive disease is a significant risk to life and this is where vaccination is aimed. The highest incidence of invasive pneumococcal disease occurs in adults over 65, in children under 2 years, and in those with impaired immunity, as listed in Box 1. Invasive pneumococcal disease is more common in winter and spring.

• Bacteraemia (live bacteria in the blood) without a known site of infection accounts for around 70% of invasive disease in children under 2 years.³ Bacteraemia is present in around 5% of young children with fever above 39°C without another source. Bacteraemia can progress rapidly to septicaemia, a more significant blood infection associated with capillary leak, shock and increased risk of mortality.
• Bacteraemic pneumonia accounts for around 15% of invasive pneumococcal disease among children under two, and is the most common bacterial pneumonia in this age group. Pneumococcal empyema (pus in a body cavity, e.g. the pleural space) is a common complication, particularly in developing countries.
• Pneumococcal meningitis. The pneumococcus became the leading cause of bacterial meningitis among children under 5 years of age once Hib vaccination was introduced. Before the introduction of pneumococcal vaccination, children under 1 year had the highest rates of pneumococcal meningitis, approximately 10 cases per 100,000 population per year. Incidence in all age groups has been reduced to around 10% of this figure. This is a catastrophic condition: 5-10% of affected children will die and over a quarter will develop permanent neurologic sequelae. In children with impaired immunity (box 1) the figures are much higher.
• Osteomyelitis/septic arthritis: is a less common presentation, but pneumococci are responsible for around 10% of cases of osteomyelitis and septic arthritis.

RISK FACTORS: WHO GETS INVASIVE DISEASE?

Apart from the under-2s and over-65s, susceptibility to infection is increased by conditions that impair the integrity of the lower respiratory tract, (e.g. influenza, passive smoking). Children with impaired immunity (Box 1) are at very high risk.

Attendance at nursery doubles the risk of invasive disease and acute otitis media.

Children with cochlear implants are at increased risk of pneumococcal meningitis.

The risk of invasive disease is also greater in children of Afro-Caribbean, Native American and Native Alaskan ethnicity.

Otitis media and bacteremia are most common in children aged 6 months to 2 years.

Sinusitis is most common in children 2 years and older.

Pneumonia and meningitis are most common in children under 5 years.

Signs and Symptoms

The signs and symptoms of pneumococcal infections depend on the site of the infection.

MANAGEMENT OF PNEUMOCOCCAL DISEASE

Management depends on the site and sensitivities of the infection and on the severity of the case. Antibiotics and supportive care are needed, and for invasive disease this will usually mean a hospital admission.

Penicillin resistance is increasing amongst circulating pneumococcal strains. However, beta-lactam antibiotics (e.g. amoxicillin, cefuroxime) achieve high levels in middle ear fluid and the respiratory tract. They are therefore the drugs of choice for otitis media (OM) and sinusitis, even in the face of penicillin-resistant pneumococci.

Amoxicillin is the drug of choice for most noninvasive disease. If otitis media fails to respond after high-dose amoxicillin, the next option is usually augmentin. The recommended treatment regimes are:

• OM or sinusitis (initial treatment) – amoxicillin for 5-10 days (otitis media) or 10-21 days (sinusitis)
• OM or sinusitis that does not improve – High-dose amoxicillin, amoxicillin-clavulanate (augmentin), cefuroxime, or ceftriaxone (IM)
• In penicillin allergy, azithromycin (or other macrolide) or cefuroxime may be used, although local guidelines may vary. Many pneumococcal strains are resistant to erythromycin.

PREVENTION, PREVENAR AND PNEUMOVAX³

Vaccination aims to protect those groups in whom pneumococcal infection is likely to be more common and/or more serious. The two vaccines are inactivated, and do not contain live organisms or the organomercury vaccine preservative, thiomersal. The only contraindication to their use is previous severe allergic response to the same vaccine, which is very rare.

Since the introduction of routine vaccination there has been a large reduction in both invasive and non-invasive disease incidence due to vaccine serotypes in both vaccinated and in older unvaccinated populations (due to herd protection), although there has been an increase in invasive disease due to nonvaccine serotypes.

Pneumovax® 23 is a polysaccharide vaccine protective against 23 serotypes which account for about 96% of all serious invasive infection in the UK. It is not very effective in infants under 2 years whose immune systems are less mature. Older children and adults do respond, and although not as well as to the conjugate vaccines, most develop a good immune response within three weeks of a single dose.

The antibody response in young children can be improved by conjugating the polysaccharide vaccine to proteins.

Prevenar® 13 is a conjugate vaccine that was introduced to the childhood immunisation schedule in 2010. (The previous vaccine, Prevenar® 7, protected against seven serotypes). It is immunogenic from age two months and protects against thirteen of the most common pneumococcal serotypes.

The UK childhood immunisation schedule consists of a primary course of two doses of Prevenar, at least two months apart, and a third dose in the second year of life. A single dose is also recommended for children aged over 12 months and under five years of age who didn’t have the vaccine as a baby, or who weren’t given the full course of three doses.

Children over 2 years but under 5 years in at-risk groups will usually be given a single dose of Pneumovax II, at least two months after their third dose of Prevenar 13. Children considered to be at higher risk are shown in Box 1. Detailed recommendations on vaccination in at risk groups are given in the Green Book.³

SUMMARY

The pneumococcus occurs widely in human populations who often carry it asymptomatically and who exchange serotypes with one another over time. Whilst this is mostly harmless, there is a significant possibility of serious, invasive disease with life threatening consequences. At risk groups include very young children and those whose immunity is compromised. The introduction of vaccination against the pneumococcus has significantly reduced the disease burden and fatality rate in the developed world, but herd immunity is an important part of this and it is important to keep vaccination rates high. Over time more may need to be done as the pneumococcus adapts and resistant non-vaccine strains emerge.

REFERENCES

1. WHO Pneumococcal disease http://www.who.int/immunization/topics/pneumococcal_disease/en/

2. Roche A, Heath PT, Sharland M et al: Prevalence of nasopharyngeal carriage of pneumococcus in preschool children attending day care in London. Arch Dis Child. 2007 Dec; 92(12): 1073–1076

3. The Green Book Chapter 25; Pneumococcal: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/263318/Green-Book-Chapter-25-v5_2.pdf