Discovery and Validation of Biomarkers to Guide Clinical Management of Pneumonia in African Children

Huang, H., Ideh, R. C., Gitau, Evelyn, Thezenas, M. L., Jallow, M., Ebruke, B., Chimah, O., Oluwalana, C., Karanja, H., Mackenzie, G., Adegbola, R. A., Kwiatkowski, D., Kessler, B. M., Berkley, J. A., Howie, S. R. C. and Casals-Pascual, C. (2014) 'Discovery and Validation of Biomarkers to Guide Clinical Management of Pneumonia in African Children'. Clinical Infectious Diseases, Vol 58, Issue 12, pp. 1707-1715.

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Abstract

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.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 460 Genomics. Proteomics QY Clinical Pathology > QY 4 General works WB Practice of Medicine > WB 102 Clinical medicine WS Pediatrics > Diseases of Children and Adolescents > By System > WS 280 Respiratory system
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1093/cid/ciu202
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	10 Apr 2015 10:01
Last Modified:	15 Jun 2018 14:45
URI:	https://archive.lstmed.ac.uk/id/eprint/5075

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