Bacterial Infections, Fever, Viral Infection
Conditions
Keywords
fever in infants under 3 months, Viruses, Respiratory infection multiplex PCR, Virome
Brief summary
Fever in infants younger than 3 months is a common reason for emergency department visits and is associated with a significant risk of serious bacterial infections. Because it is difficult to distinguish bacterial from viral infections at presentation, management is often aggressive and includes invasive procedures, hospitalization, and empiric antibiotic therapy. Despite advances in molecular diagnostics, the etiology of fever remains unidentified in a substantial proportion of cases. This study aims to assess the presence of pathogenic viruses in respiratory and intestinal samples from febrile infants younger than 3 months compared with afebrile controls, and to explore associations with clinical, biological, environmental, and socio-economic factors
Detailed description
Fever in infants under three months of age is a high-stakes clinical condition because severe bacterial infections occur in up to 20-25% of cases, while clinical signs alone cannot reliably distinguish bacterial from viral illness. Due to immune immaturity, management is often aggressive, involving hospitalization, lumbar puncture, and intravenous antibiotics. Although molecular diagnostics (multiplex PCR), bacterial biomarkers (CRP, procalcitonin), and clinical algorithms have improved care, approximately one quarter of cases still lack a confirmed etiology-most often because viral infections are difficult to definitively establish. This research project aims to improve etiological diagnosis in febrile young infants by systematically evaluating multiplex molecular tests and novel host-response biomarkers (including interferon-induced proteins) using minimally invasive nasal swabs. By correlating these results with final clinical diagnoses-classified as confirmed or probable viral or bacterial infections-the study seeks to clarify the role of these diagnostic tools in early infancy. Seasonal variations as well as environmental and socio-economic factors will be analyzed. A biological sample collection will be constituted for future analyses.The ultimate goal is to enhance diagnostic precision, reduce unnecessary hospitalizations and antibiotic exposure, and optimize the management of febrile infants.
Interventions
BIOLOGICALbiological samples
Nasal cavity swab (multiplex RT-PCR respiratory viral panel) Stool sample or peri-anal swab Blood sampling (700 µL EDTA + capillary drop for MxA testing) Biomarker analysis (CRP, PCT, MxA, CD169, CD14, CD64, HLA-DR)
Sponsors
University Hospital, Montpellier
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Masking description
Viral infections are epidemic and strongly seasonal. Therefore, we plan to include children during both the autumn-winter and spring-summer periods. Two groups will be constituted: Period A (spring-summer): May 2 to August 31 - 50 febrile infants included. Period B (autumn-winter): October 1 to February 28 - 50 febrile infants included.
Intervention model description
This is a prospective, single-center RIPH-2 study. Two groups of subjects will be recruited: One group of febrile infants (n = 100) One group of control infants (n = 30) Patients will be recruited from the pediatric emergency department in Montpellier. Control subjects will be enrolled through an existing pathway at the Montpellier University Hospital (CHU de Montpellier), as part of preoperative assessments.
Eligibility
Sex/Gender
ALL
Age
0 Months to 3 Months
Healthy volunteers
Yes
Inclusion criteria
: For participants : * Age \< 3 months * Fever ≥38°C confirmed in pediatric emergency department For control group : * Age \< 3 months * Children requiring general anesthesia or managed in the pediatric emergency department, or during hospitalization or consultation, for a non-infectious condition requiring venipuncture
Exclusion criteria
: For participants : * Lack of parental/legal guardian consent * Lack of affiliation with a social security scheme * Antibiotic treatment within 8 days prior to inclusion For control group : * Lack of parental/legal guardian consent * Lack of affiliation with a social security scheme * Antibiotic treatment within 8 days prior to inclusion * Infectious episode within 8 days prior to inclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of detection of pathogenic viruses in nasal cavity samples | Day 0 | Proportion of infants with at least one pathogenic virus detected by multiplex RT-PCR in nasal cavity samples. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of viral detection rates between febrile infants and controls | Day 0 | Viruses known to be pathogenic include: RSV, Influenza A, Influenza B, COVID-19, Parainfluenza virus (types 1, 2, 3, and 4), Rhinovirus, Coronavirus 229, Coronavirus NL63, Coronavirus OC43, Enterovirus, Adenovirus, Bocavirus, Metapneumovirus |
| Comparison of viruses associated with fever in infants under 3 months of age according to the final diagnosis (viral-origin fever vs bacterial-origin fever) in nasal swabs and stool samples and/or perianal swabs | Day 0 | Final clinical diagnosis categories: * Confirmed bacterial infection: Identification of a bacterial pathogen in a normally sterile site (by culture, antigen testing, or PCR). * Probable bacterial infection: No pathogen identified in a sterile site, but clinical evidence supporting bacterial infection (signs of sepsis or localized infection) and/or elevated bacterial biomarkers (CRP \> 20 mg/L, PCT \> 0.5 ng/L), with favorable response to antibiotic therapy. * Probable viral infection: No virus identified and no evidence supporting bacterial infection. * Confirmed viral infection: Identification of at least one pathogenic virus, with compatible clinical manifestations and no evidence supporting bacterial infection. |
| Analysis of biological markers of inflammation | Day 0 | Inflammatory markers analyzed include: CRP, PCT, MxA, plasma CD14, and cellular markers (CD169, CD14, CD64, HLA-DR) |
| Correlation between the presence and number of pathogenic viruses and environmental and socioeconomic factors. | Day 0 | Environmental factors: Living environment, number of rooms in the household, and number of people living in the home. Socioeconomic factors: Daycare attendance, number of siblings, and parents' occupations |
| Establishment of a biological sample collection (biobank) | At the inclusion | Study of the bacterial virome integrated into a separately funded project entitled "Metagenomics for a Closer Look at Early-Life Exposures to Viruses." |
Countries
France
Contacts
CONTACTEric JEZIORSKI, PU PH
Outcome results
None listed