Plasmodium falciparum Breath Metabolomics (Breathomics) Analysis as a Non-Invasive Practical Method to Diagnose Malaria in Pediatric
Children under 5 years of age are particularly vulnerable to malaria. Malaria has caused 445,000 deaths worldwide. Currently, rapid diagnostic tests (RDTs) are the fastest method to diagnose malaria. However, there are limitations that exist such as low sensitivity in detecting infections with low parasitemia. Practical, non-invasive and high ability tests to detect parasite are needed to find specific biomarkers for P. falciparum infection to determine the potential of P. falciparum 4 thioether in breathomics analysis by GC-MS as a practical non-invasive method in diagnosing malaria in pediatrics. Literature reviews from Google Scholar and ProQuest were published no later than the last 5 years. The concept of breathomics is that the breath’s volatile organic compounds (VOCs) profile is altered when the health condition changes. Breath samples from individuals infected with P. falciparum malaria were taken by exhalation. Through GC-MS analysis, it was found that 4 thioether compounds (allyl methyl sulfide (AMS), 1-methylthio-propane, (Z) -1-methylthio-1-propene and (E) -1-methylthio-1-propene) underwent a significant change in concentration during the infection. Based on experiments conducted on mice and humans, the breathomics method is known to be able to detect parasitemia levels up to <100 parasites/µL, has a sensitivity level of about 71% to 91% and a specificity of about 75% to 94%. The discovery of 4 thioether compounds by GC-MS is a strong indication of malaria, because it has the potential for high sensitivity and specificity, and the detection power exceeds the ability of RDTs.
World Health Organization. (2016). Malaria in children under five. [online] Available at: http://www.who.int/malaria/areas/high_risk_groups /children/en/ [Accessed 23 Feb. 2018]. [Internet]. Apps.who.int. 2019 [cited 15 December 2019]
Kelly, M., Su, C., Schaber, C., Crowley, J., Hsu, F., Carlson, J. and Odom, A. Malaria Parasites Produce Volatile Mosquito Attractants. mBio. 2015;6(2), .e00235-15
Busula, A., Bousema, T., Mweresa, C., Masiga, D., Logan, J., Sauerwein, R., Verhulst, N., Takken, W. and de Boer, J. Gametocytemia and Attractiveness of Plasmodium falciparum–Infected Kenyan Children to Anopheles gambiae Mosquitoes. J Infect Dis. 2017;216(3), 291-295
Labtestsonline.org. Malaria [Internet]. 2015 [cited 2018 Feb 19]. Available from:https://labtestsonline.org/conditions/malaria
Labtestsonline.org. Malaria [Internet]. 2015 [cited 2018 Feb 19]. Available from: https://labtestsonline.org/conditions/malaria 6. Malwest.gr. Laboratory diagnosis [Internet]. 2018 [cited 2018 Feb 19]. Available from: http://www.malwest.gr/enus/malaria/informationfor healthcareprofessionals/laboratorydiagnosis.aspx
Rapid-diagnostics.org. RDT Info: Advantages and disadvantages [Internet]. 2018 [cited 2018 Feb 19]. Available from: http://www.rapiddiagnostics.org/ app_advan.htm
Beale D, Jones O, Karpe A, Dayalan S, Oh D, Kouremenos K, et al. A Review of Analytical Techniques and Their Application in Disease Diagnosis in Breathomics and Salivaomics Research. Int J Mol Sci. 2016: 23;18(12):24
Bujak R, Struck-Lewicka W, Markuszewski MJ, Kaliszan R. Metabolomics for laboratory diagnostics. J Pharm Biomed Anal. 2015 Sep;113:108–20
Emwas A-H, Luchinat C, Turano P, Tenori L, Roy R, Salek RM, et al. Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review. Metabolomics. 2015 Aug;11(4):872–94
Murphy S C, Shott J P, Parikh S, Etter P, Prescott W R and Stewart VA. Review article: malaria diagnostics in clinical trials Am. J. Trop. Med. Hyg. 2013; 89: 824–39
Berna AZ, McCarthy JS, Wang RX, Saliba KJ, Bravo FG, Cassells J, et al. Analysis of Breath Specimens for Biomarkers of Plasmodium falciparum Infection. J Infect Dis. 2015 Oct 1;212(7):1120–8 13. Ahmed WM, Lawal O, Nijsen TM, Goodacre R, Fowler SJ. Exhaled Volatile Organic Compounds of Infection: A Systematic Review. ACS Infect Dis. 2017 Oct 13;3(10):695–710 14. Fidock DA. A Breathprint for Malaria: New Opportunities for Non-Interventional Diagnostics and Mosquito Traps? J Infect Dis. 2018 15. Pereira J, Porto-Figueira P, Cavaco C, Taunk K, Rapole S, Dhakne R, et al. Breath Analysis as a Potential and Non-Invasive Frontier in Disease Diagnosis: An Overview. Metabolites. 2015 Jan 9;5(4):3–55
Amir A, Cheong F-W, De Silva JR, Lau Y-L. Diagnostic tools in childhood malaria. Parasit Vectors [Internet]. 2018 [cited 2018 Feb 15];11(1). Available from: https://parasitesandvectors.biomedcentral.com/a rticles/10.1186/s13071-018-2617-y
Wong RP, Flematti GR, Davis TM. Investigation of volatile organic biomarkers derived from Plasmodium falciparum in vitro. Malar J. 2012;11(1):314
Trowell S, Berna A, Padovan B, Locke V. Methods of detecting plasmodium infection. 2018
Capuano R, Domakoski AC, Grasso F, Picci L, Catini A, Paolesse R, et al. Sensor array detection of malaria volatile signature in a murine model. Sens Actuators B Chem. 2017 Jun;245:341–51
Maltha J, Gillet P, Jacobs J. Malaria rapid diagnostic tests in travel medicine. Clin Microbiol Infect. 2013 May;19(5):408–15.
Pathsoc.org [internet]. 2013 [cited 2018 Feb 19] Available from: https://www.pathsoc.org/files/ meetings/2016NottinghamPresentations/MolPat hTT%205%20Monks.pdf 22. Lawal O, Ahmed W, Nijsen T, Goodacre R and Fowler S. Exhaled breath analysis: a review of ‘breath-taking’ methods for off-line analysis. Metabolomics. 2017 Aug; 13(10)
Correa R, Coronado L, Garrido A, DurantArchibold A and Spadafora C. Volatile organic compounds associated with Plasmodium falciparum infection in vitro. 2017; 10:215
Buffinton GD, Hunt NH, Cowden WB, Clark IA. Detection of short-chain carbonyl products of lipid peroxidation from malaria-parasite (Plasmodium vinckei)-infected red blood cells exposed to oxidative stress. Biochem J. 1988;249(1):63–8
Vallejo AF, Martínez NL, González IJ, ArévaloHerrera M, Herrera S. Evaluation of the loop mediated isothermal DNA amplification (LAMP) kit for malaria diagnosis in P. vivax endemic settings of Colombia. PLoS Negl Trop Dis. 2015;9:e3453
Das S, Peck RB, Barney R, Jang IK, Kahn M, Zhu M, et al. Performance of an ultra-sensitive Plasmodium falciparum HRP2-based rapid diagnostic test with recombinant HRP2, culture parasites, and archived whole blood samples. Malar J. 2018;17:118
de Boer J, Robinson A, Powers S, Burgers S, Caulfield J, Birkett M, Smallegange R, van Genderen P, Bousema T, Sauerwein R, Pickett J, Takken W and Logan J. Odours of Plasmodium falciparum-infected participants influence mosquito-host interactions. Scientific Reports. 2017: (1)
McCarthy JS Griffin PM Sekuloski S, et al. . Experimentally induced blood-stage plasmodium vivax infection in healthy volunteers. J Infect Dis 2013; 208:1688–94
Schaber C, Katta N, Bollinger L, Mwale M, MlothaMitole R, Trehan I, Raman B and Odom John, A. Breathprinting Reveals Malaria-Associated Biomarkers and Mosquito Attractants. J Infect Dis. 2018
Risticevic S, Lord H, Górecki T, Arthur CL, Pawliszyn J. Protocol for solid-phase microextraction method development. Nat Protoc. 2010 Jan;5(1):122– 39
Batista EPA, Costa EFM, Silva AA. Anopheles darlingi (Diptera: Culicidae) displays increased attractiveness to infected individuals with Plasmodium vivax gametocytes. Parasit Vectors. 2014; 10.1186/1756-3305-7-251 32.
Peled N, Hakim M, Bunn PA Jr., et al. Noninvasive breath analysis of pulmonary nodules. J Thorac Oncol. 2012; 7: 1528-1533
Chambers ST, Bhandari S, Scott-Thomas A, Syhre M. Novel diagnostics: progress toward a breath test for invasive Aspergillus fumigatus. Med Mycol. 2011 Apr;49(S1):S54–61
De Moraes CM, Stanczyk NM, Betz HS, Pulido H, Sim DG, Read AF, et al. Malaria-induced changes in host odors enhance mosquito attraction. Proc Natl Acad Sci. 2014 Jul 29;111(30):11079–84 35. Lee TMN Huang LS Johnson MK, et al. . In vitro metabolism of piperaquine is primarily mediated by CYP3A4. Xenobiotica. 2012; 42:1088–95
The Indonesian Journal of Tropical and Infectious Disease (IJTID) is a scientific peer-reviewed journal freely available to be accessed, downloaded, and used for research. All articles published in the IJTID are licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, which is under the following terms:
Attribution — You must give appropriate credit, link to the license, and indicate if changes were made. You may do so reasonably, but not in any way that suggests the licensor endorses you or your use.
NonCommercial — You may not use the material for commercial purposes.
ShareAlike — If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original.
No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.