Multi-Omics Advancements towards Plasmodium vivax Malaria Diagnosis
Abstract
:1. Introduction
1.1. Grounding and Current Status of Malaria Diagnostics
1.2. Multi-Omics Approaches in Malaria Diagnosis
2. Challenges in the Development of Diagnostic Tools for P. vivax and P. falciparum
3. Recent Advancements in Multi-Omics Based Malaria Diagnosis
- Malaria parasites show a vast difference on their molecular level resulting in unique life cycle stages such as hypnozoites in P. vivax and P. ovale.
- There is a paucity of accurate, reliable, rapid, and pathogen species differentiating diagnostic assays in endemic regions of the world.
- Delayed diagnosis contributes to the augmentation of resistant strains and antimalarial drugs facilitate the selection of mutants, aggravating the condition.
- Advancements in malaria diagnosis are propelled by advancements in technology and omics fields.
- The dearth of understanding about the pathogen results in a scarcity of promising diagnostic or therapeutic targets.
- Omics-based understanding of the pathogen or host response may facilitate understanding of the pathogenesis.
- Integration of multiple omics facilitates a holistic view of pathobiology and highlights crucial biomolecules for diagnostic and therapeutic purposes.
4. Approaches to Integrative Multi-Omics
5. Advantage of Multi-Omics Approaches
6. Limitation in Multi-Omics Approaches
7. Current Challenges and Future Opportunities
- A biomarker or tool is necessary for the differentiation of malaria-causing pathogen species in humans with high sensitivity and specificity.
- A biomarker or methodology is necessary for the diagnosis of asymptomatic malaria patients and hypnozoite carriers for eliminating the parasite reservoir from the host.
- There is inaccessibility of the P. vivax parasite for comprehensive analysis of the pathogen due to low parasitemia in clinical samples.
- There is an inability to grow P. vivax continuously in the in vitro cell culture condition.
- The paucity of complete proteomic and metabolomic databases of P. vivax is one of the major roadblocks in the quest for a diagnostic, differentiation, and prognostic biomarker search.
- There is a lack of annotation of the genome of P. vivax. Most of the genes are hypothetical, uncharacterized, or unannotated.
- There is a lack of clinical information with heterogeneity information such as gender, race, age, and geographic location to understand the vivax malaria severity.
- There is a lack of information on the correlation between parasitemia and the severity of vivax malaria.
- The coupled diagnosis of G-6-PD deficiency class along with P. vivax for the efficient treatment and elimination of the parasite reservoir from the host system.
8. Concluding Remarks and Future Perspective
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | Microscopy | Polymerase Chain Reaction | Rapid Diagnostic Test |
---|---|---|---|
Sensitivity (parasite/µL) | 4 to 20 [30] | 0.7 [30] | 100 to 500 [30] |
Differentiation of strains | Difficult (No) | Yes | Yes |
Time to results | Moderately time-consuming | Very time consuming | Instant results |
Reliability | Moderate | High | Low |
Expertise | Moderate | High | Low |
Cost | Low | High | Low |
Stability | Moderate | High | Low |
Infrastructure | Minimal | Required | Minimal |
S.No. | Omics | Target Biomolecule | Methodology | Species | Sensitivity (%) | Specificity (%) | Limit of Detection (Parasite/µL) | Ref. |
---|---|---|---|---|---|---|---|---|
1 | Phenome | iRBCs | Microscopy | Pv and Pf | 84.30 | 90.80 | 50 | [35,36] |
2 | Phenome | iRBCs | Attenuated total reflectance Infrared spectroscopy (ATR-IR) | Pf and Pv | 92 | 97 | 0.5 | [37] |
3 | Phenome | iRBCs | Quantitative Buffy Coat (QBC) Test | Pf and Pm | 55.9 | 88.8 | 1000 | [38] |
4 | Genome | 18S rRNA | Nested PCR | Pf, Pv, Po, Pm | 98.5 | 94.3 | 1–2 Pf and 5–10 Pv | [39,40] |
5 | Genome | 18S rRNA | Loop-mediated isothermal amplification (LAMP) | Pf and Pv | 98.5 | 94.3 | 365 | [40,41] |
6 | Genome | cytochrome c oxidase III | Multiplex single-tube nested PCR (M.S.T.N.P.C.R.) | Pf, Pv, Po, Pm, Pk | 88.7 | 100 | 0.3 Pf | [42] |
7 | Proteome | pLDH | Immunochromatographic microfluidic device (IMD) | Pf and Pan | 100 | >85 | 87 Pf, 174 Pv | [7,43] |
8 | Proteome | pLDH and PfHRPII | Rapid diagnostic tests (RDT) | Pf and Pan | 100 | >85 | 500 | [44] |
9 | Inorganic biocrystal | Hemozoin | Micro N.M.R. | Pf | 97.90 | 90 | <10 | [3,5] |
10 | Inorganic biocrystal | Hemozoin | Surface-enhanced Raman spectroscopy (S.E.R.S.) using butterfly-wing nanostructures | Pf 3D7 | NA | NA | 25 | [30] |
11 | Inorganic biocrystal | Hemozoin | Magneto-optical technology (M.O.T.) using polarized light | Pf, Pv, Po, Pm | 78.3 | 74.4 | 600 | [45] |
12 | Inorganic biocrystal | Hemozoin | Cell Dyn machine | Pf, Pv, Po, Pm | 93 | 97 | 27.786 | [46] |
13 | Metabolome | Retinol | LC-MS | Pv | NA | NA | NA | [47] |
14 | Metabolome | Pipecolic acid | LC-MS | Pv, Pf | NA | NA | NA | [48] |
15 | Metabolome | Hippuric acid | LC-MS | Pv, Pf | NA | NA | NA | [48] |
Genomics/Epigenetics | Proteomics | Metabolomics | Phenomics | |
---|---|---|---|---|
Strength | Has SNP level information and indicates the effect of environmental factors on gene expression. The most stable as compared to other omics. With advancements in NGS, the cost has declined for gene-based diagnostics. | Has different outcome variations, modulating unit of phenome. | Modulating biomolecules are highly dynamic; ideal for indicating prognosis. | Leads to easier detection, morphology-centric. |
Weakness | Gene deletion or mutations due to various factors may change the identification status of a gene; it does not correlate with the amount of protein produced. | The final product of gene expression may lack information on SNPs or copy numbers of a gene. Does not correlate with all the SNPs and gene transcript levels. The method is low-cost effective. | Highly dynamic biomolecules may get converted to byproducts if not handled with care; byproducts may not be disease drivers. The method is low-cost effective. | Artifacts and morphological changes don’t represent changes due to pathogen confidently; any intracellular parasite may deform the RBCs. |
Opportunity | Facilitates understanding of SNPs-based antimalarial resistance such as k13 polymorphs and provides haplotyping and mapping of parasite strain origin mapping. SNP-based severity is a possibility, such as G6PD deficiency for Primaquine-based treatment. Helps the preparation of a customized/predicted proteome database for new proteins. Low-cost, efficient, and accurate diagnostics may soon be delivered to low economic regions of endemic states. | Provides insight into the immune response against pathogens for vaccine purposes, i.e. pathways affected and effector proteins for drug targets. The receptor-based study suggests the potential interacting pathways for establishing pathogenesis. | Highly dynamic, representative of slightest stimulus making it best prognostic biomarker candidate. No traces of post-infection clearance. | Quick diagnosis; basic staining, and microscopy may be used to check the deformities. |
Threat | Gene deletion in parasites may lead to false-negative results such as pfHRPII based RDTs. Genetic mutants do not translate to proteins, hence proteomics of mutants is essential to understand. | Antibody traces remain long before the infection is cleared, resulting in false positives. Post-translation modifications may help in understanding cascade regulation for pathobiology. | Highly dynamic, resulting in a quick byproduct formation under in vitro situations that might not be related to pathobiology. Samples are high maintenance and require freezing of biomolecules as soon as samples are procured. | Artifacts may lead to false results and require an expert to differentiate the different characteristic features for reliable results. |
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Aggarwal, S.; Peng, W.K.; Srivastava, S. Multi-Omics Advancements towards Plasmodium vivax Malaria Diagnosis. Diagnostics 2021, 11, 2222. https://doi.org/10.3390/diagnostics11122222
Aggarwal S, Peng WK, Srivastava S. Multi-Omics Advancements towards Plasmodium vivax Malaria Diagnosis. Diagnostics. 2021; 11(12):2222. https://doi.org/10.3390/diagnostics11122222
Chicago/Turabian StyleAggarwal, Shalini, Weng Kung Peng, and Sanjeeva Srivastava. 2021. "Multi-Omics Advancements towards Plasmodium vivax Malaria Diagnosis" Diagnostics 11, no. 12: 2222. https://doi.org/10.3390/diagnostics11122222
APA StyleAggarwal, S., Peng, W. K., & Srivastava, S. (2021). Multi-Omics Advancements towards Plasmodium vivax Malaria Diagnosis. Diagnostics, 11(12), 2222. https://doi.org/10.3390/diagnostics11122222