Diagnosis of Mycoplasma Pneumoniae Infection With Detection of Specific Antibody-secreting Cells in Community-acquired Pneumonia (CAP) Patients of the Randomised Placebo-controlled Multi-centre Effectiveness Trial of Adjunct Betamethasone Therapy (myKIDS-STEP)
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|ClinicalTrials.gov Identifier: NCT04043325|
Recruitment Status : Recruiting
First Posted : August 2, 2019
Last Update Posted : August 2, 2019
|Condition or disease||Intervention/treatment|
|Community-acquired Pneumonia||Diagnostic Test: Specific antibody-secreting cell (ASC) enzyme-linked immunspot (ELISpot) assay|
Community-acquired pneumonia (CAP) is a common serious infection and a leading cause of hospitalisation in children. Knowledge about the underlying pathogen is a major unmet clinical need, particularly in CAP caused by Mycoplasma pneumoniae (Mp). Timely and reliable identification is critical for initiating effective and tailored antimicrobial treatment. However, determining the causative pathogen of childhood CAP is complicated by the low yield of blood cultures and difficulty obtaining specimens from the lower respiratory tract of children. Therefore, clinicians attempt to detect potential pathogens in upper respiratory tract (URT) specimens, knowing that children carry viruses and bacteria in their URT that may or may not be causative for the current pneumonia episode. Consequently, the interpretation of diagnostic tests performed with URT specimens is limited and may lead to unnecessary antimicrobial prescriptions.
The hurdle in differentiating infection from carriage was documented recently for Mp, a frequently reported pathogen underlying CAP in children worldwide (up to 20-40% during epidemics). Current diagnostic tests, including polymerase chain reaction (PCR) of URT specimens or serology, do not reliable differentiate between Mp infection and carriage. Mp is found in the URT in up to 56% of healthy children. These findings challenge recent epidemiological data indicating Mp as the most common bacterial cause of CAP, in up to 23% of hospitalized U.S. children aged 10-17 years. A ≥4-fold increase in IgG antibody levels is still considered the "gold standard" for diagnosing M. pneumoniae infection, but has low sensitivity when e.g. compared with IgM seroconversion and/or a 2-fold IgM increase. In fact, such a definition is also not helpful in acute clinical management, as it requires acute and convalescent sera.
Circulating antigen-specific B cell responses have been investigated in vaccine studies and demonstrated to be more rapid and shorter lived than antibody responses. After exposure, antigen-specific B cells proliferate and differentiate into antibody-secreting cells (ASCs) and memory B cells. ASCs transiently circulate in the peripheral blood in the first days after an antigen encounter. In a recent observational pilot study of children with CAP and healthy controls, we showed that the detection of Mp-specific immunoglobulin (Ig) M ASCs by enzyme-linked immunospot (ELISpot) assay re-classified 15% of PCR-positive and 12% of IgM-seropositive study participants (https://doi.org/10.1164/rccm.201904-0860LE). Thus, the measurement of specific IgM ASCs by ELISpot assay is an innovative, minimally invasive, and rapid test method that optimises diagnosis of Mp CAP in children.
In view of these promising first results, the aim of this study is to establish the diagnosis of Mp infection by the measurement of Mp-specific ASCs by ELISpot in CAP patients enroled in the randomised placebo-controlled multi-centre effectiveness trial of adjunct betamethasone therapy (KIDS-STEP study, Protocol ID: NCT03474991).
|Study Type :||Observational|
|Estimated Enrollment :||100 participants|
|Official Title:||Diagnosis of Mycoplasma Pneumoniae Infection With Detection of Specific Antibody-secreting Cells in Community-acquired Pneumonia (CAP) Patients of the Randomised Placebo-controlled Multi-centre Effectiveness Trial of Adjunct Betamethasone Therapy (myKIDS-STEP)|
|Actual Study Start Date :||May 20, 2019|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
- Diagnostic Test: Specific antibody-secreting cell (ASC) enzyme-linked immunspot (ELISpot) assay
Clinical samples (nasopharyngeal swabs and max. 5 ml blood) will be collected from patients enroled in the KIDS-STEP study (NCT03474991; children aged 1-10 years) at enrolment (day 1), at day 3, and at day 28.Other Names:
- Specific enzyme-linked immunosorbent assay (ELISA)
- Specific polymerase chain reaction (PCR)
- Detection of Mp-specific IgM ASCs by ELISpot assay [ Time Frame: Day 1 (at enrolment) ]Diagnosis of Mp infection in CAP patients of the KIDS-STEP study with the detection of Mp-specific IgM ASCs by ELISpot assay at enrolment (day 1).
- No detection of Mp-specific IgM ASCs by ELISpot assay [ Time Frame: Day 28 ]Longitudinal assessment of levels of Mp-specific IgM ASCs by ELISpot assay.
- Detection of Mp-specific DNA by PCR [ Time Frame: Day 28 ]Longitudinal assessment of levels of Mp-specific DNA by PCR.
- Detection of Mp-specific IgM by ELISA [ Time Frame: Day 28 ]Longitudinal assessment of levels of Mp-specific IgM by ELISA.
- Detection of specific IgM ASCs against other pathogens by ELISpot assay [ Time Frame: Day 1 ]Diagnosis of infection with other respiratory pathogens than Mp in CAP patients of the KIDS-STEP study with the detection of specific IgM ASCs by ELISpot assay at enrolment (day 1).
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04043325
|Contact: Patrick M. Meyer Sauteur, MD PhDfirstname.lastname@example.org|