Invasive Encapsulated Bacterial Infections: Investigations to Detect Immune Deficiency


These guidelines have been produced to guide clinical decision making for the medical, nursing and allied health staff of Perth Children’s Hospital. They are not strict protocols, andthey do not replace the judgement of a senior clinician. Clinical common-sense should be applied at all times. These clinical guidelines should never be relied on as a substitute for proper assessment with respect to the particular circumstances of each case and the needs of each patient. Clinicians should also consider the local skill level available and their local area policies before following any guideline.

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To provide guidance on the recommended first-line investigations for children with invasive encapsulated bacterial infections (IEBI) such as Streptococcus pneumoniae (invasive pneumococcal disease, IPD), Neisseria meningitidis (meningococcal disease) or Haemophilus influenzae, to detect underlying immune disorders that may increase the risk of recurrent and/or severe IEBI.


Invasive encapsulated bacterial infections (IEBI) are a leading cause of bacterial meningitis and septicaemia in children worldwide.1,2 While hospitalisation rates for IEBI in children have fallen significantly since the introduction of conjugate vaccines against these bacteria3,4, there are still over 50 cases per year of IPD in WA children.5

Children with immunodeficiency and other chronic diseases are at significantly increased risk of IPD6 and defects in humoral immunity (antibody and complement deficiencies, and asplenia) are the most commonly identified primary immunodeficiencies in children and young adults with IEBI.7-9

While these guidelines focus on the investigation for immune deficiency in children with IEBI, there are many other potential clinical presentations of children with immunodeficiency. These guidelines should be considered in conjunction with other resources such as the ASCIA Primary Immunodeficiencies Clinical Update, RCH Clinical Practice Guidelines for Primary Immunodeficiencies and Starship clinical guidelines for IPD and investigation of immune deficiency.


For this guideline, invasive encapsulated bacterial infection (IEBI) is defined as isolation or detection of Streptococcus pneumoniae, Neisseria meningitidis or Haemophilus influenzae from sterile sites (blood, cerebrospinal fluid, (CSF), joint / bone or pleural fluid, but not sputum or middle ear fluid) by culture or polymerase chain reaction (PCR).

Key points


For all children presenting with IEBI, obtain a focused history to identify and record potential risk factors:

  • Vaccination status
  • Pre-existing conditions – CSF leak, asplenia, congenital heart disease, diabetes, Down syndrome, renal failure
  • Implanted material (cochlear implant, external ventricular drain etc.)
  • Previous history of IEBI
  • Secondary immunodeficiency (medications, malignancy, human immunodeficiency virus (HIV) infection, autoimmune disease)
  • Personal or family history of primary immunodeficiency (PID)

First line investigations

Recommended for all children with IEBI (unless a predisposing condition is already confirmed):

  • Full blood count (FBC) and manual blood film examination for Howell Jolly bodies
  • IgG, IgM and IgA
  • HIV serology (HIV 1/2 Ab/Ag assay)
  • CH50 and AH50 (complement function testing), C3 and C4
  • Mannose binding lectin (MBL)
  • Splenic ultrasound

Blood collection timing, sample and handling requirements

In patients likely to have a prolonged admission due to severe disease, investigations can be requested after resolution of the acute severe phase of illness. In children with less severe disease, investigations can be arranged to coincide with any other planned venepuncture prior to discharge.

Sample requirements:

  • 2 x SST (gold top) tubes – 2 mL blood volume in each tube. Send directly to lab
    • One serum tube must be centrifuged and frozen in two aliquots within 1 hour of collection for CH50/AH50. Second tube for immunoglobulins, HIV serology
  • 1 x EDTA (purple top) tubes – 1 mL blood volume for FBC and blood film

When to refer

In any patient where there is clinical concern about a possible underlying immunodeficiency, including if investigations are normal or not yet performed, please contact the PCH Immunologist on-call.

Other reasons to consider referral may include:

  • children with an atypical presentation or clinical course of the acute episode
  • children with a history of frequent infections, or any previous invasive bacterial infection
  • children with a family history of invasive bacterial infection
  • children with signs of chronic disease including failure to thrive, clubbing or splenomegaly
  • children with any abnormal results of first line investigations

Follow up

  • The primary clinical team who are caring for a patient with IEBI are responsible for follow up of the results of investigations performed in accordance with these guidelines.
    • If there are any abnormal results the primary team should refer the child to PCH Immunology, or to Infectious Diseases in cases of asplenia or HIV.
  • The treating team can contact the PCH Immunologist or Infectious Diseases Physician on call via PCH Switchboard (08 6456 2222) at any time, regardless of investigation results, to discuss any clinical concerns.

Vaccination recommendations

To reduce the risk of future infections, individuals with IEBI should ensure they are up to date with routine vaccinations (see Immunisation schedule and catch-up immunisations) and are recommended to receive additional vaccinations as listed below, as per the Western Australian Immunisation Schedule for people with medical risk conditions (MRC).

A previous episode of invasive pneumococcal disease (IPD) is known to be a MRC as specified in the Australian Immunisation Handbook (The Australian Immunisation Handbook). There is limited evidence regarding the risk of future invasive infections in people with a previous episode of an IEBI other than IPD. Until such evidence does emerge, we suggest that the immunisation recommendations for children with a previous episode of IPD be followed for all children with any IEBI and be expanded to include protection against meningococcal disease.

Where possible, recommended vaccines should be given opportunistically at discharge from hospital. A plan for subsequent vaccinations should be included in the discharge summary and given to the family to complete in the community or through the Stan Perron Immunisation centre at PCH.


  1. Chan J, Gidding HF, Blyth CC, Fathima P, Jayasinghe S, McIntyre PB, et al. Levels of pneumococcal conjugate vaccine coverage and indirect protection against invasive pneumococcal disease and pneumonia hospitalisations in Australia: An observational study. PLOS Medicine. 2021;18(8):e1003733.
  2. Sadarangani M. Protection Against Invasive Infections in Children Caused by Encapsulated Bacteria. Front Immunol. 2018;9:2674.
  3. Martin NG, Sadarangani M, Pollard AJ, Goldacre MJ. Hospital admission rates for meningitis and septicaemia caused by Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in children in England over five decades: a population-based observational study. Lancet Infect Dis. 2014;14(5):397-405.
  4. Jayasinghe S, Menzies R, Chiu C, Toms C, Blyth CC, Krause V, et al. Long-term Impact of a “3 + 0” Schedule for 7- and 13-Valent Pneumococcal Conjugate Vaccines on Invasive Pneumococcal Disease in Australia, 2002–2014. Clinical Infectious Diseases. 2017;64(2):175-83.
  5. Directorate CDC. Department of Health WA;  [Available from:
  6. Pelton SI, Weycker D, Farkouh RA, Strutton DR, Shea KM, Edelsberg J. Risk of Pneumococcal Disease in Children With Chronic Medical Conditions in the Era of Pneumococcal Conjugate Vaccine. Clinical Infectious Diseases. 2014;59(5):615-23.
  7. Gaschignard J, Levy C, Chrabieh M, Boisson B, Bost-Bru C, Dauger S, et al. Invasive Pneumococcal Disease in Children Can Reveal a Primary Immunodeficiency. Clinical Infectious Diseases. 2014;59(2):244-51.
  8. Butters C, Phuong LK, Cole T, Gwee A. Prevalence of Immunodeficiency in Children With Invasive Pneumococcal Disease in the Pneumococcal Vaccine Era: A Systematic Review. JAMA Pediatr. 2019;173(11):1084-94.
  9. Sanges S, Wallet F, Blondiaux N, Theis D, Vérin I, Vachée A, et al. Diagnosis of primary antibody and complement deficiencies in young adults after a first invasive bacterial infection. Clinical Microbiology and Infection. 2017;23(8):576.e1-.e5
Approved by: Clinical Practice Advisory Committee
Date: July 2023
Endorsed by: Nurse, Co-director Surgical Services
Date: July 2023

Review date: July 2026

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