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Abstract
Introduction Clinically diagnosed pneumonia in children is a leading cause of paediatric hospitalisation and mortality. The aetiology is usually bacterial or viral, but malaria can cause a syndrome indistinguishable from clinical pneumonia. There is no method with high sensitivity to detect a bacterial infection in these patients and, as result, antibiotics are frequently overprescribed. Conversely, unrecognised concomitant bacterial infection in patients with malarial infections occur with omission of antibiotic therapy from patients with bacterial infections. Previously, we identified two combinations of blood proteins with 96% sensitivity and 86% specificity for detecting bacterial disease. The current project aimed to validate and improve these combinations by evaluating additional biomarkers in paediatric patients with clinical pneumonia. Our goal was to describe combinations of a limited number of proteins with high sensitivity and specificity for bacterial infection to be incorporated in future point-of-care tests. Furthermore, we seek to explore signatures to prognosticate clinical pneumonia.
Methods and analysis Patients (n=900) aged 2–59 months presenting with clinical pneumonia at two Gambian hospitals will be enrolled and classified according to criteria for definitive bacterial aetiology (based on microbiological tests and chest radiographs). We will measure proteins at admission using Luminex-based immunoassays in 90 children with definitive and 160 with probable bacterial aetiology, and 160 children classified according to the prognosis of their disease. Previously identified diagnostic signatures will be assessed through accuracy measures. Moreover, we will seek new diagnostic and prognostic signatures through machine learning methods, including support vector machine, penalised regression and classification trees.
Ethics and dissemination Ethics approval has been obtained from the Gambia Government/Medical Research Council Unit The Gambia Joint Ethics Committee (protocol 1616) and the institutional review board of Boston University Medical Centre (STUDY00000958). Study results will be disseminated to the staff of the study hospitals, in scientific seminars and meetings, and in publications.
Trial registration number H-38462.
- respiratory infections
- diagnostic microbiology
- paediatric infectious disease & immunisation
- paediatric thoracic medicine
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Footnotes
PLH and GAM contributed equally.
Contributors The study concept and design were conceived by CV, GAM and PLH with contributions from EFK, WdJ, AAD, RCW, JR, MAM, UDA and QB. Acquisition of clinical data were defined by CV, GAM, PLH, YAO, YSI, RS, SG, SK and AJ. Acquisition of laboratory data was defined by CV, RS, EFK, WdJ, RCW, MAM and GAM. The analytical plan was conceived by CV. Participant enrolment and follow-up will be conducted by YAO and YSI under direct supervision of GAM and oversight from PLH, SK, AJ and QB. Sample processing and diagnostic laboratory assays will be supervised by RS and data management by SG. All on-the-ground operations in the Gambia will be directly supervised by GM and overseen by CV. QB will be one of the clinicians assigning participants to one of the probable diagnostic groups. The multiplex immunoassay to quantify proteins will be conducted by EFK with inputs from CV, WdJ, RCW, JR and MAM. Analysis will be performed by CV. CV prepared the first draft of the manuscript with inputs from GAM, PLH, YAO, YSI, RS and SG. CV, YAO, YAI, RS, SG, EFK, SK, AJ, QB, WDJ, AAD, RCW, JR, MAM, UDA, PLH and GAM provided edits, reviewed and approved the final version of the manuscript, providing substantial intellectual contributions.
Funding This study will be supported by the National Institutes of Health of the USA (R21AI140258) and will leverage resources from the project entitled ‘Will the Ongoing Use of a Two-Dose, Rather Than Three-Dose Schedule of Pneumococcal Conjugate Vaccine, Have Similar Impact in Rural Gambia’ study funded by the Joint Global Health Trials scheme (MRC UK, Welcome, UK AID, UK National Institute for Health Research) and the Bill and Melinda Gates Foundation.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.