Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04043325 |
| Other study ID # |
2019-00425 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 20, 2019 |
| Est. completion date |
December 31, 2021 |
Study information
| Verified date |
November 2020 |
| Source |
University Children's Hospital, Zurich |
| Contact |
Patrick M. Meyer Sauteur, MD PhD |
| Phone |
+41442667896 |
| Email |
patrick.meyer[@]kispi.uzh.ch |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
To compare presence and kinetics of Mycoplasma pneumoniae (Mp)-specific immunoglobulin (Ig) M
antibody-secreting cells (ASCs) with Mp DNA and Mp-specific IgM antibodies in patients with
community-acquired pneumonia (CAP) of the KIDS-STEP study.
Description:
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).
