Evaluation of Pathogenesis and Diagnosis of Mycoplasma Pneumoniae Community-acquired Pneumonia (CAP) (myCAP)

The Role of Adaptive Immune Responses to Mycoplasma Pneumoniae in Pathogenesis and Diagnosis of Community-acquired Pneumonia (CAP) in Children: an Observational Single-center Study (myCAP Study)

To investigate the Mycoplasma pneumoniae-specific circulating antibody-secreting cell (ASC) response and Mycoplasma pneumoniae-specific interferon (INF)-γ-secreting T cell response, along with polymerase chain reaction (PCR) and serology, in a cohort of children with community-acquired pneumonia (CAP) and controls.

Study Overview

• Status: Completed
• Conditions: Diagnosis; Childhood Pneumonia; Mycoplasma Pneumonia; Antibody-secreting Cells; Enzyme-linked Immunospot (ELISpot)
• Intervention / Treatment: Diagnostic test: Enzyme-linked immunospot (ELISpot) assay [Blood]

• Study Type: Observational
• Enrollment (Actual): 490

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

CAP cohort:

There will be a consecutive ongoing recruitment through the project leader or instructed physicians of the department of infectious diseases and emergency in daily clinical practice.

Healthy control cohort:

The project leader will be informed by the local surgeons about a planned elective surgical procedure, unrelated to respiratory tract disease, and will include children during the pre-operation discussion. Samples will be collected by the anaesthesist prior to the start of the surgical procedure, while the child is under general anaesthesia and has an intravenous line. In a subgroup of such children undergoing planned adenotomy, the removed adenoids will be collected after surgery.

Family control cohort:

Family members will be included simultaneously with the index CAP patients.

Description

Inclusion Criteria:

CAP cohort:

• Children of age 3 to 18 years;
• In- and outpatients;
• Clinically diagnosed community-acquired pneumonia (CAP);

Healthy control cohort:

- Healthy asymptomatic children of age 3 to 18 years undergoing an elective surgical procedure;

Family control cohort:

- Family members of index CAP patients.

Exclusion Criteria:

• Hospital-acquired pneumonia;
• Immunodeficiencies;
• Chronic lung disorders.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CAP cohort; Children of age 3 to 16 years;; In- and outpatients;; Clinically diagnosed community-acquired pneumonia (CAP).	Diagnostic test: Enzyme-linked immunospot (ELISpot) assay [Blood]; The ASC ELISpot will be developed based on the improved methods recently described [Nat Protoc 2013;8:1073-87]. This protocol allows rapid (6-8 h) detection of specific ASCs in small volumes (1-2 ml) of blood. M. pneumoniae protein P1 (50 μl/ml) will be used as antigen. The optimal concentration of coating antigen will be assessed in advance in two-fold serial dilutions for clear spot definition. The M. pneumoniae-specific T cell ELISpot will be developed based on methods recently described [Nat Protoc 2009;4:461-9].; Other Names: Polymerase chain reaction (PCR) [Pharyngeal swab specimens]; Enzyme-linked immunosorbent assay (ELISA) [Serum]
Healthy control cohort; Healthy asymptomatic children of age 3 to 16 years;; undergoing an elective surgical procedure.	Diagnostic test: Enzyme-linked immunospot (ELISpot) assay [Blood]; The ASC ELISpot will be developed based on the improved methods recently described [Nat Protoc 2013;8:1073-87]. This protocol allows rapid (6-8 h) detection of specific ASCs in small volumes (1-2 ml) of blood. M. pneumoniae protein P1 (50 μl/ml) will be used as antigen. The optimal concentration of coating antigen will be assessed in advance in two-fold serial dilutions for clear spot definition. The M. pneumoniae-specific T cell ELISpot will be developed based on methods recently described [Nat Protoc 2009;4:461-9].; Other Names: Polymerase chain reaction (PCR) [Pharyngeal swab specimens]; Enzyme-linked immunosorbent assay (ELISA) [Serum]
Family control cohort; - Family members of index CAP patients.	Diagnostic test: Enzyme-linked immunospot (ELISpot) assay [Blood]; The ASC ELISpot will be developed based on the improved methods recently described [Nat Protoc 2013;8:1073-87]. This protocol allows rapid (6-8 h) detection of specific ASCs in small volumes (1-2 ml) of blood. M. pneumoniae protein P1 (50 μl/ml) will be used as antigen. The optimal concentration of coating antigen will be assessed in advance in two-fold serial dilutions for clear spot definition. The M. pneumoniae-specific T cell ELISpot will be developed based on methods recently described [Nat Protoc 2009;4:461-9].; Other Names: Polymerase chain reaction (PCR) [Pharyngeal swab specimens]; Enzyme-linked immunosorbent assay (ELISA) [Serum]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in numbers of M. pneumoniae-specific ASCs and M. pneumoniae-specific INF-γ-secreting T cells in blood from inclusion (day 0) to 1-month follow-up (day 28)	Enzyme-linked immunospot (ELISpot) assay and flow cytometry	At day 0 (inclusion, disease presentation) and at day 28 (follow-up, disease resolution)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in M. pneumoniae DNA levels in respiratory samples from inclusion (day 0) to 1-month follow-up (day 28)	PCR	At day 0 (inclusion, disease presentation) and at day 28 (follow-up, disease resolution)
Change in total and M. pneumoniae-specific antibody levels (immunoglobulin (Ig)G, IgM, IgA) from inclusion (day 0) to 1-month follow-up (day 28)	Enzyme-linked immunosorbent assay (ELISA)	At day 0 (inclusion, disease presentation) and at day 28 (follow-up, disease resolution)
Outcome of community-acquired pneumonia (CAP) assessed by clinical assessment of body temperature (°C) and respiratory rate (per minute) at 1-month follow-up (day 28)	Clinical assessment of body temperature (°C) and respiratory rate (per minute), with worse outcome defined as body temperature more than 38.5°C and respiratory rate according to age more than 40/min for 3 years, more than 34/min for 4-5 years, more than 30/min for 6-12 years, and more than 16/min for 13-18 years.	At day 28 (follow-up)

Collaborators and Investigators

• Sponsor: University Children's Hospital, Zurich
• Investigators: Principal Investigator: Patrick M. Meyer Sauteur, MD, University Children's Hospital, Zurich

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): October 31, 2020
• Study Completion (Actual): October 31, 2020

Study Registration Dates

• First Submitted: July 6, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pleural Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pneumonia, Bacterial; Pleurisy; Mycoplasmatales Infections; Disease; Pneumonia; Pleuropneumonia; Mycoplasma Infections; Pneumonia, Mycoplasma
• Other Study ID Numbers: 2016-00148

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Not yet defined.

Drug and device information, study documents

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