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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Discovery and validation of biomarkers to guide clinical management of pneumonia in african children
Clinical Infectious Diseases, Volume 58, No. 12, Year 2014
Notification
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Description
Background. Pneumonia is the leading cause of death in children globally. Clinical algorithms remain suboptimal for distinguishing severe pneumonia from other causes of respiratory distress such as malaria or distinguishing bacterial pneumonia and pneumonia from others causes, such as viruses. Molecular tools could improve diagnosis and management.Methods. We conducted a mass spectrometry-based proteomic study to identify and validate markers of severity in 390 Gambian children with pneumonia (n = 204) and age-, sex-, and neighborhood-matched controls (n = 186). Independent validation was conducted in 293 Kenyan children with respiratory distress (238 with pneumonia, 41 with Plasmodium falciparum malaria, and 14 with both). Predictive value was estimated by the area under the receiver operating characteristic curve (AUC).Results. Lipocalin 2 (Lpc-2) was the best protein biomarker of severe pneumonia (AUC, 0.71 [95% confidence interval,. 64-.79]) and highly predictive of bacteremia (78% [64%-92%]), pneumococcal bacteremia (84% [71%-98%]), and "probable bacterial etiology" (91% [84%-98%]). These results were validated in Kenyan children with severe malaria and respiratory distress who also met the World Health Organization definition of pneumonia. The combination of Lpc-2 and haptoglobin distinguished bacterial versus malaria origin of respiratory distress with high sensitivity and specificity in Gambian children (AUC, 99% [95% confidence interval, 99%-100%]) and Kenyan children (82% [74%-91%]).Conclusions. Lpc-2 and haptoglobin can help discriminate the etiology of clinically defined pneumonia and could be used to improve clinical management. These biomarkers should be further evaluated in prospective clinical studies. © 2014 The Author.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC4036688/bin/supp_58_12_1707__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC4036688/bin/supp_ciu202_ciu202supp.pdf
Authors & Co-Authors
Huang, Honglei
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Ideh, Readon C.
Gambia
Child Survival Theme
Gitau, Evelyn N.
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Kenya, Nairobi
Kenya Medical Research Institute
Thézénas, Marie Laëtitia
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Jallow, Muminatou
Gambia
Child Survival Theme
Ebruke, Bernard Ese
Gambia
Child Survival Theme
Chimah, Osaretin U.
Gambia
Child Survival Theme
Oluwalana, Claire
Gambia
Child Survival Theme
Karanja, Henry K.
Kenya, Nairobi
Kenya Medical Research Institute
MacKenzie, Grant Austin
Gambia
Child Survival Theme
Adegbola, Richard A.
Gambia
Child Survival Theme
Kwiatkowski, Dominic P.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Kessler, Benedikt M.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Berkley, James A.
United Kingdom, Oxford
Nuffield Department of Medicine
Kenya, Nairobi
Kenya Medical Research Institute
Howie, Stephen R.C.
Gambia
Child Survival Theme
Casals-Pascual, Climent
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Statistics
Citations: 54
Authors: 16
Affiliations: 5
Identifiers
Doi:
10.1093/cid/ciu202
ISSN:
10584838
e-ISSN:
15376591
Research Areas
Infectious Diseases
Maternal And Child Health
Study Design
Cohort Study