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NCID > For Healthcare Professionals > Diseases and Conditions > Pneumococcal Disease (Invasive)

Pneumococcal Disease (Invasive)

Pneumococcal Disease (Invasive)

Causative agent

Streptococcus pneumoniae (also known as pneumococcus)

Incubation Period

Not well defined as colonization usually precedes invasive disease; may be as short as 1 to 3 days.

Infectious Period

Presumably as long as pneumococci are carried in oro-nasal secretions in asymptomatic individuals (colonization usually lasts weeks to months); with penicillin treatment, persons infected with susceptible strains are rendered non- infectious within 24-48 hours.

Transmission

Respiratory droplets and direct contact with respiratory secretions of an infected person (usually requires frequent or prolonged close contact).

Epidemiology

S. pneumoniae is one of the most common causes of invasive infections such as bacteraemia, meningitis and bacteraemic pneumonia, and bacterial mucosal infections such as sinusitis and otitis media. Of the 91 pneumococcal serotypes, 23 account for the vast majority of invasive pneumococcal disease (IPD) in humans. The worldwide emergence of pneumococcal resistance to antibiotics, including beta- lactams, macrolides, tetracycline, cotrimoxazole and fluoroquinolones has been a considerable concern.

Invasive pneumococcal infection is defined as the isolation of S. pneumoniae from normally sterile sites such as blood, pleural fluid and cerebrospinal fluid (CSF). Pneumococcal pneumonia is considered an invasive disease but would be excluded if blood or pleural fluid cultures are sterile. Otitis media is not considered an invasive disease, but may be included if S. pneumoniae is isolated from normally sterile middle ear fluid.

In Singapore, the mean annual hospitalisation rate for IPD from 2000-2008 was 8.9 per 100,000 population (about 380 cases per year). A total of 157 deaths from IPD were reported during this period, of which 5 were under the age of 5 years. In 2009, there were 251 reported cases of IPD. Of these, 124 met the criteria for IPD. The highest incidence rate was in children < 5 years of age and the elderly aged 65 years and above. In children, serotypes 14, 6B, 23F, 19F, 6A and 19A were the most common strains isolated, and accounted for 89% of all invasive diseases in children <5  years  old.  However,  in  adults,  isolate  distribution  was  more  spread  out and common ones were 14, 3, 6B, 8 and 19F which accounted for 51% of all invasive diseases. Mean case fatality rates for IPD in single-centre series were 6.1% in children but rising to 30% in children with pneumococcal meningitis; while in adults, this was 21.4%.

A pneumococcal polysaccharide vaccine (23-valent or serotype) has been available locally since 1988. It was recommended for children >2 years old with risk factors for IPD and adults >65 years old, but its immunogenicity was fair and its uptake was very poor. However, it would cover 82.8% of IPD serotypes in adults. A highly immunogenic pneumococcal conjugate vaccine (7-valent) was licensed locally for children 6 weeks to 9 years old since 2002 but became commercially available locally only since late 2005, with uptake primarily in children <5years within the private sector. In November 2009, it became the 10th vaccine-preventable disease to be included in the National Childhood Immunization Programme.


  • Typically between 40-50% of children and 20-30% of adults carry pneumococci asymptomatically in their nasopharynx.
  • Infection is often preceded by a respiratory viral illness before local disease (from congestion and concentration of virulent pneumococci) or invasion leading to systemic or invasive disease
  • Can infect any organ.
  • Mucosal infections include acute otitis media, bacterial sinusitis, conjunctivitis.
    • Otitis media may be complicated by mastoiditis and intracranial extension with abscess formation.
    • Sinusitis may be complicated by periorbital or orbital cellulitis, with resultant intracranial extension.
  • Common deep-seated or invasive infections include primary bacteraemia, pneumonia (with or without bacteraemia; pneumonia without bacteraemia is not traditionally classified as “invasive”), and meningitis.
    • Pneumonias may be complicated by parapneumonic effusions and empyemas.
    • Meningitis is infrequently associated with development of subdural empyemas, intracranial abscesses and vasculitic/ thrombotic phenomena.
  • Less commonly, it can also cause osteomyelitis, pyogenic arthritis, endocarditis, myocarditis, pericarditis, bacterial peritonitis, endophthalmitis and salpingitis.
  • In some patients (especially those who are immunocompromised), pneumococcal infections may be fulminant and present with overwhelming sepsis and multi-organ failure.

Risk Factors:

  • Age (<5 years and >65 years)
  • Racial predisposition (though not evident in local series)
  • Chronic illnesses (chronic respiratory, heart, renal and liver disease, alcoholism, diabetes)
  • Cochlear implants
  • Cerebrospinal fluid leaks
  • Functional or anatomic asplenia/ splenic dysfunction (including sickle cell disease)
  • Immunocompromised—either congenital, acquired (e.g. HIV infection) or iatrogenic via immunosuppression.


  • Microbiological confirmation by culture remains the gold standard for diagnosis and allows for sensitivity testing as well as subsequent serotyping; however the yield in blood may be low for different pneumococcal syndromes—high in meningitis, low (around 25%) in pneumonia.
    • The volume of inoculum (usually blood, uncommonly pleural fluid or CSF) is important, and blood cultures (if positive) are usually positive within 18 hours of inoculation
  • Gram stains and latex agglutination testing of infected body fluids (e.g. CSF, pleural, peritoneal or joint fluid) should always be performed and may be helpful, although other streptococci may also appear as Gram-positive diplococci and latex agglutination testing lacks sensitivity.
  • Urinary pneumococcal cell wall polysaccharide (antigen) testing is currently available and a positive result is strongly suggestive of  pneumococcal disease/ pneumonia in adults, although it can be positive in the setting of acute nasopharyngeal carriage (as often occurs in children) and hence the specificity is much poorer in children.
  • Imaging (e.g. X-ray, computerised tomography, ultrasound, and nuclear or magnetic resonance imaging) assists in localising infection in patients with appropriate clinical symptoms and signs

A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 or electronically via CD-LENS) not later than 72 hours from the time of diagnosis.



  • Appropriate resuscitation, oxygenation and invasive or supportive care as required; the importance of this cannot be overemphasized.
  • Initial choice of empirical antibiotics should be guided by local age- appropriate guidelines for respective clinical syndromes (by institution or college).
  • Once confirmed microbiologically, appropriate, targeted antibiotic treatment should be guided by susceptibility testing after the initial empirical regime.
    • Penicillins (followed by 1st and 2nd generation cephalosporins) are the preferred choice of antimicrobials; however, depending on the site of infection, much higher doses may be required, or 3rd generation cephalosporins may be used (e.g. meningitis).
    • Where pneumococci are resistant to beta-lactams, treatment may be individualized with vancomycin, quinolones or tetracyclines as appropriate.
  • Source control (e.g. drainage of infections in closed spaces like empyemas or cerebral abscesses) are often critical to success or failure of antibiotic treatment.
  • Adjunct therapies may also need to be considered e.g. dexamethasone in pneumococcal meningitis, activated protein C in severe pneumococcal sepsis


  • All children <2 years old should receive pneumococcal conjugate vaccine as recommended under the National Childhood Immunization Program.
    • Children <1 year old should receive 2 primary doses at 3 months and 5 months followed by a booster at 1-2 years.
    • Children >1 year old should receive age appropriate doses of pneumococcal conjugate vaccine and also depending on whether they have risk factors for IPD.
  • All adults ≥65 years old, and persons 2 to 64 years with risk factors for IPD (as above) should receive 23-valent pneumococcal polysaccharide vaccine as recommended by MOH.
  • All childhood vaccinations should be notified to the National Immunisation Registry, Health Promotion Board. All post vaccination adverse reactions should also be notified to the Pharmacovigilance Branch, Health Sciences Authority.









References

  1. O’Brien KL, Wolfson LJ, Watt JP et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 2009; 374:893-902
  2. van der Poll T, Opal SM. Pathogenesis, treatment and prevention of pneumococcal pneumonia. Lancet 2009; 374:1543-56
  3. Low S, Chan F L F, Cutter J et al. A national study of the epidemiology of pneumococcal disease among hospitalised patients in Singapore: 1995 to 2004. Singapore Med J 2007; 48:824-9
  4. Chong CY, Thoon KC, Mok YH et al. Invasive pneumococcal disease in Singapore children. Vaccine 2008; 26:3427-31
  5. Hsu LY, Lui SW, Lee JL et al. Adult invasive pneumococcal disease pre- and peri-pneumococcal connjugate vaccine introduction in a tertiary hospital in Singapore. J Med Microbiol 2009; 58:101-4
  6. Musher DM. Streptococcus pneumoniae. In Mandell GL, Bennet JE, Dolin R (eds). Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Churchill Livingstone; 2010:2623-42.
  7. Ministry of Health. Vaccination against pneumococcal disease. Epidemiol News Bulletin 2010; 36: 7-15.
  8. Ministry of Health. Laboratory-based surveillance system of invasive pneumococcal diseases in Singapore: a nationwide monitoring of vaccine serotype coverage. Epidemiol News Bulletin 2010;36: 40-5.





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