Clinical trial NCT03996967: Diagnostic and Prognostic Biomarkers for Childhood Bacterial Pneumonia
Official title: Diagnostic and Prognostic Biomarkers for Childhood Bacterial Pneumonia in Sub-Saharan Africa
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pneumonia, Bacterial
Viral Infection
Clinical Pneumonia
Plasmodium Falciparum Malaria
Malaria
Infections, Respiratory
Keywords: Biosignature proteins
Luminex®-based immunoassays
Point-of-care test
Children
Sub-Saharan Africa
Diagnostic Biomarkers
Prognostic Biomarkers
Mediators of Inflammation
Lead sponsor: Boston University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Medical Research Council Unit, The Gambia, LSTMH
name: Laboratory of Transnational Immunology, UMC Utrecht
First posted: 2019-06-25
Enrollment: 837
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will be enrolling children 2 month-5 years of age who seek treatment for clinical pneumonia at two hospitals in rural Gambia: Basse and Bansang hospitals

Brief summary: Clinical pneumonia is a leading cause of pediatric hospitalization. The etiology is generally bacterial or viral. Prompt and optimal treatment of pneumonia is critical to reduce mortality. However, adequate pneumonia management is hampered by: a) the lack of a diagnostic tool that can be used at point-of-care (POC) and promptly and accurately allow the diagnosis of bacterial disease and b) lack of a prognostic POC test to help triage children in need of intensive assistance. Antibiotic therapy is frequently overprescribed as a result of suspected bacterial infections resulting in development of antibiotic resistance. Conversely, in malaria-endemic areas, antibiotics may also be "underprescribed" and children with bacterial pneumonia sent home without antibiotic therapy, when the clinical pneumonia is mistakenly attributed to a co-existing malaria infection.

The investigators previously identified combinations of protein with 96% sensitivity and 86% specificity for detecting bacterial disease in Mozambican children with clinical pneumonia. The investigators' prior work showed that it is possible to identify biosignatures for diagnosis and prognosis using few proteins. Recently, other authors also identified different accurate biosignatures (e.g., IP-10, TRAIL and CRP).

In this study, the investigators propose to validate and improve upon previous biosignatures by testing prior combinations and seeking novel combinations of markers in 900 pediatric inpatients aged 2 months to 5 years with clinical pneumonia in The Gambia. The investigators will also use alternative case criteria and seek diagnostic and prognostic combination of markers. This study will be conducted in Basse, rural Gambia, in two hospitals associated with the Medical Research Council Unity The Gambia (MRCG). Approximately 900 pediatric patients with clinical pneumonia aged 2 months to 5 years of age will be enrolled. Patients will undergo standard of care test and will have blood proteins measured through Luminex®-based immunoassays.

Results of this study may ultimately support future development of an accurate point-of-care test for bacterial disease to guide clinicians in choices of treatment and to assist in the prioritization of intensive care in resource-limited settings.


Eligibility criteria: Inclusion criteria Clinical Pneumonia Patients

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

* Pediatric patients aged between 2 months and 5 years presenting at the screening sites with respiratory symptoms, i.e. cough or difficulty breathing AND
* One of the following: Increased respiratory rate for age OR indrawing OR SaO2 \< 93% OR grunting OR MUAC \< 11.5 if child is greater or equal than 6 months of age OR visible wasting AND
* Referred to clinician review for probable admission

Definition of increased respiratory rate (rr) for age based on the WHO criteria: respiratory rate (rr) \> \> 50 for 2-11 month old; rr \> 40 for 1-5 years old.

Inclusion criteria Healthy Controls

* No symptoms or signs of any disease
* No malaria infection as detected by microscopy or RDT
* No history of clinical pneumonia or hospital admission

Exclusion criteria Clinical Pneumonia Patients

An individual who meets any of the following criteria will be excluded from participation in this study:

* Suspected tuberculosis based on history of cough lasting \> 2 weeks
* Hospital admission in the previous 2 weeks.
* Children that show any evidence of other conditions that could be worsened by blood collection will be further excluded from this study.

Exclusion criteria Healthy Controls

• Having received a vaccine within the prior 4 weeks

Primary outcomes:
measure: Definitive diagnosis of an invasive bacterial disease (versus viral and malarial infection)
timeFrame: At admission
measure: Poor prognosis of clinical pneumonia
timeFrame: 30 days from admission
Secondary outcomes:
measure: Probable bacterial pneumonia (versus viral pneumonia or severe malaria)
timeFrame: At admission
measure: Oxygen saturation curve
timeFrame: Within the first 5 days of admission
measure: Need to switch antibiotic therapy
timeFrame: Within the first 3 days of admission
measure: Duration of hospital admission
timeFrame: Within 3 days of hospital discharge
measure: Time to start feeding well
timeFrame: Within the first 5 days of admission
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston University School of Public Health
state: Massachusetts
city: Basse Santa Su
country: Gambia
facility: Basse Field Station, Medical Research Council Gambia Unit
state: URR
city: Utrecht
country: Netherlands
facility: Laboratory of Transnational Immunology, UMC Utrecht
Study officials:
affiliation: Boston University
name: Clarissa Valim, MD ScD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston University
name: Patricia Hibberd, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: