TY - JOUR
T1 - Seeking diagnostic and prognostic biomarkers for childhood bacterial pneumonia in sub-Saharan Africa
T2 - study protocol for an observational study
AU - Valim, Clarissa
AU - Olatunji, Yekin Ajauoi
AU - Isa, Yasir Shitu
AU - Salaudeen, Rasheed
AU - Golam, Sarwar
AU - Knol, Edward F
AU - Kanyi, Sheriffo
AU - Jammeh, Abdoulie
AU - Bassat, Quique
AU - de Jager, Wilco
AU - Diaz, Alejandro A
AU - Wiegand, Roger C
AU - Ramirez, Julio
AU - Moses, Marsha A
AU - D'Alessandro, Umberto
AU - Hibberd, Patricia L
AU - Mackenzie, Grant A
N1 - Funding Information:
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.
Publisher Copyright:
© Author(s) (or their employer(s)) 2021.
PY - 2021/9/30
Y1 - 2021/9/30
N2 - 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.
AB - 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.
KW - diagnostic microbiology
KW - paediatric infectious disease & immunisation
KW - paediatric thoracic medicine
KW - respiratory infections
UR - http://www.scopus.com/inward/record.url?scp=85116545275&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2020-046590
DO - 10.1136/bmjopen-2020-046590
M3 - Review article
C2 - 34593486
SN - 2044-6055
VL - 11
SP - 1
EP - 10
JO - BMJ Open
JF - BMJ Open
IS - 9
M1 - e046590
ER -