Dataset Information

High-Sensitivity C-Reactive Protein: A Potential Ancillary Biomarker for Malaria Diagnosis and Morbidity.

ABSTRACT: Background:Malaria remains an important cause of morbidity and mortality in Africa. Previous studies that assessed C-reactive protein (CRP) have centered on the conventional method. This study evaluated the usefulness of high-sensitivity CRP (hs-CRP) in malaria diagnosis and morbidity in a pediatric population in Ghana. Methodology:A total of 267 subjects (100 microscopically proven nonmalarial parasitaemics as controls and 167 plasmodium parasitaemic subjects as cases), between the ages of 7 months and 18 years, were recruited for this case-control study. Blood samples were collected for malaria parasite density by microscopic examination; full blood count, electrolytes, and liver function tests using an automated analyzer; and hs-CRP levels by sandwich ELISA method. Results:The median hs-CRP concentration was lowest in the control group and increased significantly from low to high parasitaemia. The median hs-CRP level was significantly higher in high malaria parasitaemia compared to moderate and low malaria parasitaemia. Increasing hs-CRP cutoff (3.12-4.64?mg/L) presented with increasing specificity (79.3-93.1%) and sensitivity (96.4%-97.4%), except for moderate parasitaemia where a decline in sensitivity (80.9%) was observed. However, hs-CRP had relatively lower PPV but high NPV at low parasitaemia while both the PPV and NPV were moderate in moderate parasitaemia. Conclusion:hs-CRP yielded a high sensitivity, specificity, and accuracy for low, moderate, and high-grade malaria, respectively, and thus may serve as an effective supplementary diagnostic and prognostic biomarker for Plasmodium parasite infection. However, hs-CRP might not be readily useful yet for diagnostic purposes in hospitals due to the relatively low PPV and NPV for low and moderate parasitaemia and thus necessitates further studies in larger cohorts.

SUBMITTER: Addai-Mensah O

PROVIDER: S-EPMC6476067 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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High-Sensitivity C-Reactive Protein: A Potential Ancillary Biomarker for Malaria Diagnosis and Morbidity.

Addai-Mensah Otchere O Annani-Akollor Max Efui ME Fondjo Linda Ahenkorah LA Anto Enoch Odame EO Gyamfi Daniel D Sallah Lorraine L Agama Dennis D Djabatey Richard R Owiredu Eddie-Williams EW

Disease markers 20190404

<h4>Background</h4>Malaria remains an important cause of morbidity and mortality in Africa. Previous studies that assessed C-reactive protein (CRP) have centered on the conventional method. This study evaluated the usefulness of high-sensitivity CRP (hs-CRP) in malaria diagnosis and morbidity in a pediatric population in Ghana.<h4>Methodology</h4>A total of 267 subjects (100 microscopically proven nonmalarial parasitaemics as controls and 167 plasmodium parasitaemic subjects as cases), between t ...[more]

PMID: 31089391

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Project description:BackgroundIn the recent years Plasmodium vivax has been reported to cause severe infections associated with mortality. Clinical evaluation has limited accuracy for the early identification of the patients progressing towards the fatal condition. Researchers have tried to identify the serum and the plasma-based indicators of the severe malaria. Discovery of MicroRNA (miRNA) has opened up an era of identification of early biomarkers for various infectious and non-infectious diseases. MicroRNAs (miRNA) are the small non-coding RNA molecules of length 19-24 nts and are responsible for the regulation of the majority of human gene expressions at post transcriptional level.MethodsWe identified the differentially expressed miRNAs by microarray and validated the selected miRNAs by qRT-PCR. We assessed the diagnostic potential of these up-regulated miRNAs for complicated P. vivax malaria. Futher, the bioinformtic analysis was performed to construct protein-protein and mRNA-miRNA networks to identify highly regulated miRNA.ResultsIn the present study, utility of miRNA as potential biomarker of complicated P. vivax malaria was explored. A total of 276 miRNAs were found to be differentially expressed by miRNA microarray and out of which 5 miRNAs (hsa-miR-7977, hsa-miR-28-3p, hsa-miR-378-5p, hsa-miR-194-5p and hsa-miR-3667-5p) were found to be significantly up-regulated in complicated P. vivax malaria patients using qRT-PCR. The diagnostic potential of these 5 miRNAs were found to be significant with sensitivity and specificity of 60-71% and 69-81% respectively and area under curve (AUC) of 0.7 (p?<?0.05). Moreover, in silico analysis of the common targets of up-regulated miRNAs revealed UBA52 and hsa-miR-7977 as majorly regulated hubs in the PPI and mRNA-miRNA networks, suggesting their putative role in complicated P. vivax malaria.ConclusionmiR-7977 might act as a potential biomarker for differentiating complicated P. vivax malaria from uncomplicated type. The elevated levels of miR-7977 may have a role to play in the disease pathology through UBA52 or TGF-beta signalling pathway.

Project description:Plasmodium knowlesi is recognised as the main cause of human malaria in Southeast Asia. The disease is often misdiagnosed as P. falciparum or P. malariae infections by microscopy, and the disease is difficult to eliminate due to its presence in both humans and monkeys. P. knowlesi infections can rapidly cause severe disease and require prompt diagnosis and treatment. No protein biomarker exists for the rapid diagnostic test (RDT) detection of P. knowlesi infections. Plasmodium knowlesi infections can be diagnosed by PCR.Phosphoethanolamine-N-methyltransferase (PMT) is involved in malaria lipid biosynthesis and is not found in the human host. The P. falciparum, P. vivax and P. knowlesi PMT proteins were recombinantly expressed in BL21(DE3) Escherichia coli host cells, affinity purified and used to raise antibodies in chickens. Antibodies against each recombinant PMT protein all detected all three recombinant proteins and the native 29 kDa P. falciparum PMT protein on western blots and in ELISA. Antibodies against a PMT epitope (PLENNQYTDEGVKC) common to all three PMT orthologues detected all three proteins. Antibodies against unique peptides from each orthologue of PMT, PfCEVEHKYLHENKE, PvVYSIKEYNSLKDC, PkLYPTDEYNSLKDC detected only the parent protein in western blots and P. falciparum infected red blood cell lysates or blood lysates spiked with the respective proteins. Similar concentrations of PfPMT and the control, PfLDH, were detected in the same parasite lysate. The recombinant PfPMT protein was detected by a human anti-malaria antibody pool.PMT, like the pan-specific LDH biomarker used in RDT tests, is both soluble, present at comparable concentrations in the parasite and constitutes a promising antimalarial drug target. PMT is absent from the human proteome. PMT has the potential as a biomarker for human malaria and in particular as the first P. knowlesi specific protein with diagnostic potential for the identification of a P. knowlesi infection.

Dataset Information

High-Sensitivity C-Reactive Protein: A Potential Ancillary Biomarker for Malaria Diagnosis and Morbidity.

Publications

High-Sensitivity C-Reactive Protein: A Potential Ancillary Biomarker for Malaria Diagnosis and Morbidity.

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