What is the Incidence of an Immune Disorder in Children With Invasive Pneumococcal Disease (IPD)?

What is the Incidence of an Immune Disorder in Children With Invasive Pneumococcal Disease (IPD)? A Prospective Cohort Study.

This is a multicentre prospective audit to determine the incidence of immunodeficiency in children with IPD.

Aims and/or research question of the project

1. To determine the incidence of primary immunodeficiency in children >2 years who present with IPD
2. To determine the types of immunodeficiency associated with IPD in children

Study Overview

• Status: Completed
• Conditions: Primary Immunodeficiency; Invasive Pneumococcal Disease, Protection Against; Invasive Pneumococcal Disease, Recurrent Isolated, 1; Invasive Pneumococcal Disease, Recurrent Isolated, 2
• Intervention / Treatment: Other: Referral to Immunology

• Study Type: Observational
• Enrollment (Actual): 380

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia
    • Lady Cilento Children's Hospital
  • New South Wales
    • Sydney, New South Wales, Australia, 2031
      • Sydney Children's Hospital
  • South Australia
    • Adelaide, South Australia, Australia
      • Adelaide Women's and Children's Hospital
  • Victoria
    • Clayton, Victoria, Australia
      • Monash Health
    • Melbourne, Victoria, Australia, 3049
      • Royal Children's Hospital
• New Zealand
  • Wellington, New Zealand
    • Capital and Coast District Health Board

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children presenting with invasive pneumococcal disease at any of the participating sites listed.

Invasive pneumococcal disease is defined by isolation by culture or PCR of Streptococcus pneumoniae from sterile sites including blood, cerebrospinal fluid (CSF), joint fluid or pleural fluid. In those patients with bacteraemia, their presentation needs to be accompanied by signs of sepsis.

Description

Inclusion Criteria:

• Children aged 0 to 18 years admitted to one of the six centres with IPD.

Exclusion Criteria:

• Children who do not fulfil the age criteria for immunological evaluation at that particular site e.g. aged <2 years at Royal Children's Hospital.
• Children with a known underlying condition predisposing to IPD i.e. nephrotic syndrome.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Children with IPD; Children with IPD will be referred for immunological evaluation. The protocol for immune work up will be the same but between centres there is variation in the age criteria for referral i.e. >2 years in some, >6 months in others.	Other: Referral to Immunology; Screening for primary immunodeficiency including splenic dysfunction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of primary immunodeficiency in children who present with invasive pneumococcal disease	This will be picked up upon prospective immunological testing, after identification of patients with invasive pneumococcal disease. A series of tests will be performed depending on the clinical opinion of the immunology team. Such tests may include lymphocyte subsets, complement function, serum immunoglobulin levels, memory B cells, vaccine antibody responses, etc.	3 years
types of immunodeficiency associated with children who present with invasive pneumococcal disease	This will be determined based on the testing performed by the immunologists.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
whether increased referrals of children who present with invasive pneumococcal disease for investigation of primary immunodeficiency facilitates early detection	This information will come from reviewing the case series of patients who are identified from this study. The incidence of those with primary immunodeficiency will be analysed against known background rates of diagnoses.	3 years

Collaborators and Investigators

• Sponsor: Murdoch Childrens Research Institute
• Collaborators: Royal Children's Hospital

Publications and helpful links

General Publications

• Gaschignard J, Levy C, Chrabieh M, Boisson B, Bost-Bru C, Dauger S, Dubos F, Durand P, Gaudelus J, Gendrel D, Gras Le Guen C, Grimprel E, Guyon G, Jeudy C, Jeziorski E, Leclerc F, Leger PL, Lesage F, Lorrot M, Pellier I, Pinquier D, de Pontual L, Sachs P, Thomas C, Tissieres P, Valla FV, Desprez P, Fremeaux-Bacchi V, Varon E, Bossuyt X, Cohen R, Abel L, Casanova JL, Puel A, Picard C. Invasive pneumococcal disease in children can reveal a primary immunodeficiency. Clin Infect Dis. 2014 Jul 15;59(2):244-51. doi: 10.1093/cid/ciu274. Epub 2014 Apr 23.
• Picard C, Puel A, Bustamante J, Ku CL, Casanova JL. Primary immunodeficiencies associated with pneumococcal disease. Curr Opin Allergy Clin Immunol. 2003 Dec;3(6):451-9. doi: 10.1097/00130832-200312000-00006.
• Alsina L, Basteiro MG, de Paz HD, Inigo M, de Sevilla MF, Trivino M, Juan M, Munoz-Almagro C. Recurrent invasive pneumococcal disease in children: underlying clinical conditions, and immunological and microbiological characteristics. PLoS One. 2015 Mar 4;10(3):e0118848. doi: 10.1371/journal.pone.0118848. eCollection 2015.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2017
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: January 20, 2019
• First Posted (Actual): January 24, 2019

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: primary immunodeficiency; streptococcus pneumoniae; invasive pneumococcal disease
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Disease Attributes; Genetic Diseases, Inborn; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumococcal Infections; Recurrence; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Immune System Diseases
• Other Study ID Numbers: 35266C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No