Diagnostic and Prognostic Biomarkers for Childhood Bacterial Pneumonia
Condition: Pneumonia, Bacterial; Viral Infection; Clinical Pneumonia; Plasmodium Falciparum Malaria; Malaria; Infections, Respiratory
MeSH terms: Infections; Communicable Diseases; Pneumonia; Malaria; Malaria, Falciparum; Virus Diseases; Pneumonia, Bacterial; Respiratory Tract Infections
Study type: Observational

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.
    


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
      
Biospecimen description: 
      Venous blood will be collected from 900 children hospitalized with pneumonia for the
      multiplex bead-based immunoassay and for tests that will be part of standard of care,
      including full blood cell count, bacterial blood culture, rapid malaria test and/or blood
      smear slide for malaria diagnosis. Also as part of standard of care in PVS, a nasopharyngeal
      swab will be collected, and analyzed in this study for viral PCR. Venous blood for the
      multiplex bead-based immunoassay will also be collected from 20 healthy controls to evaluate
      the precision of the biomarkers.
    
Keywords: Biosignature proteins; Luminex®-based immunoassays; Point-of-care test; Children; Sub-Saharan Africa; Diagnostic Biomarkers; Prognostic Biomarkers; Mediators of Inflammation