Proteomic identification of host and parasite biomarkers in saliva from patients with uncomplicated Plasmodium falciparum malaria.
BACKGROUND
Malaria cases attributed to Plasmodium falciparum account for approximately 600,000 deaths yearly, mainly in African children. The gold standard method to diagnose malaria requires the visualization of the parasite in blood. The role of non-invasive diagnostic methods to diagnose malaria remains unclear.


METHODS
A protocol was optimized to deplete highly abundant proteins from saliva to improve the dynamic range of the proteins identified and assess their suitability as candidate biomarkers of malaria infection. A starch-based amylase depletion strategy was used in combination with four different lectins to deplete glycoproteins (Concanavalin A and Aleuria aurantia for N-linked glycoproteins; jacalin and peanut agglutinin for O-linked glycoproteins). A proteomic analysis of depleted saliva samples was performed in 17 children with fever and a positive-malaria slide and compared with that of 17 malaria-negative children with fever.


RESULTS
The proteomic signature of malaria-positive patients revealed a strong up-regulation of erythrocyte-derived and inflammatory proteins. Three P. falciparum proteins, PFL0480w, PF08_0054 and PFI0875w, were identified in malaria patients and not in controls. Aleuria aurantia and jacalin showed the best results for parasite protein identification.


CONCLUSIONS
This study shows that saliva is a suitable clinical specimen for biomarker discovery. Parasite proteins and several potential biomarkers were identified in patients with malaria but not in patients with other causes of fever. The diagnostic performance of these markers should be addressed prospectively.
Wellcome Trust Centre for Human Genetics and Centre for Cellular and Molecular Physiology, Roosevelt Drive, Oxford, OX3 7BN, UK.
Honglei
H
Huang
Mukram M
MM
Mackeen
Matthew
M
Cook
Eniyou
E
Oriero
Emily
E
Locke
Marie L
ML
Thézénas
Benedikt M
BM
Kessler
Davis
D
Nwakanma
Climent
C
Casals-Pascual
D000293:Adolescent; D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D002648:Child; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000469:parasitology / Q000473:pathology; D020543:Proteome / Q000032:analysis*; D012463:Saliva / Q000737:chemistry* / Q000469:parasitology*
D015415:Biomarkers; D020543:Proteome