Biomarkers Identification from Urine of Dengue Patients Through GCMS for Initial Development of Non-Invasive Diagnostic Kit

Azura Amid; Muhamad Shirwan Abdullah Sani; Aszrin Abdullah; Norbaiyah Mohamed Bakrim; Wan Fatein Nabeila Wan Omar; Nurul Aulia Zakaria; Nor Zamzila Abdullah; Nik Nur Fatnoon Nik Ahmad

doi:10.31436/iiumej.v25i2.2785

Authors

Azura Amid International Islamic University Malaysia https://orcid.org/0000-0002-1304-7559
Muhamad Shirwan https://orcid.org/0000-0002-8202-1491
Aszrin International Islamic University Malaysia https://orcid.org/0000-0003-3049-5254
Norbaiyah https://orcid.org/0000-0002-2747-8659
Fatein https://orcid.org/0000-0002-1878-8313
Nurul Aulia Zakaria International Islamic University Malaysia
Nor Zamzila Abdullah https://orcid.org/0000-0002-7313-6545
Nik Nur Fatnoon Nik Ahmad https://orcid.org/0000-0002-5049-2686

DOI:

https://doi.org/10.31436/iiumej.v25i2.2785

Keywords:

Biomarkers, metabolites, GC/MS, dengue, detection method

Abstract

Dengue infection detection methods namely dengue serology test and Real-Time PCR are only available in clinical laboratories or healthcare facilities. This is time-consuming and inconvenient for patients. Thus, a non-invasive on-site urinary diagnostic kit for dengue infection that requires no trained personnel for blood extraction would be advantageous and warranted, albeit in developed or underdeveloped nations with limited resources. To develop the on-site diagnostic kit, an identification of biomarkers related to dengue infection is needed. This preliminary study aims to identify potential metabolite biomarkers from the urine of dengue patients using GCMS analysis. Urine samples of patients with serologically confirmed dengue infection were analyzed and compared with healthy volunteers. The study shows that the GCMS approach can identify differences in the urine of dengue patients from healthy volunteers. Heptacosane, Hexadecane, 2,4-bis(1,1-dimethylethyl) phenol, 2-bromooctane, tetradecane, hexyl octyl ester sulfurous acid, 2-benzoyl methyl ester benzoic acid, 2,9-dimethyl decane, and pentadecane were identified from the urine of dengue patients. The identified secretion of alkane may be a suitable candidate for colorimetric assay for the development of a user-friendly, home-screening rapid test kit for the detection of dengue infection.

ABSTRAK: Kaedah pengesanan jangkitan denggi seperti ujian serologi denggi dan PCR masa nyata, merupakan kaedah biasa yang digunakan di makmal klinikal atau pusat kesihatan. Ianya memakan masa dan menyukarkan pesakit. Oleh itu, kit diagnostik air kencing yang tidak invasif yang tidak memerlukan kakitangan terlatih bagi mengekstrak darah adalah sangat berguna dan diperlukan bagi mengesan jangkitan denggi, sama ada di negara maju atau tidak membangun dengan sumber terhad. Bagi membangunkan kit diagnostik ini, pengesanan penanda bio berkaitan jangkitan denggi diperlukan. Kajian awal ini bertujuan bagi mengenal pasti penanda bio metabolit yang berkaitan pada air kencing pesakit denggi dengan menggunakan analisis GC/MS. Sampel air kencing pesakit yang disahkan secara serologi telah dikaji dan dibandingkan dengan sukarelawan yang sihat. Kajian menunjukkan teknik GCMS dapat mengenal pasti perbezaan antara air kencing pesakit denggi dan sukarelawan yang sihat. Heptakosane, Hekzadekane, fenol 2,4-bis(1,1-dimetiletil), 2-bromookten, tetradekana, asid sulfurik ester heksil oktil, asid benzoik metil ester 2-benzoik, 2,9-dimetil dekana, dan pentadekana telah dikenal pasti terkumpul dalam air kencing pesakit denggi. Rembesan alkana merupakan penanda bio yang sesuai bagi ujian kolorimetrik dalam membangunkan kit ujian pantas diagnostik yang mesra pengguna bagi mengesan denggi di rumah.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

References

Wilder-Smith A, Ooi EE, and Wills B. (2019) Dengue. The Lancet, 393(10169):350–363. DOI: https://doi.org/10.1016/S0140-6736(18)32560-1

Whitehorn J, and Simmons CP. (2011) The pathogenesis of dengue. Vaccine, 29(42). doi:10.1016/j.vaccine.2011.07.022 DOI: https://doi.org/10.1016/j.vaccine.2011.07.022

Martina BEE. (2014) Dengue pathogenesis: A disease driven by the host response. Science Progress, 97(3). doi:10.3184/003685014X14049173153889 DOI: https://doi.org/10.3184/003685014X14049173153889

Woon YL, Hor CP, Lee KY, Mohd Anuar SFZ, Mudin RN, Sheikh Ahmad MK, Komari S, Amin F, Jamal R, Chen WS, Goh PP, Yeap L, Lim ZR, Lim TO. (2018) Estimating dengue incidence and hospitalization in Malaysia, 2001 to 2013. BMC Public Health, 18(1). doi:10.1186/s12889-018-5849-z DOI: https://doi.org/10.1186/s12889-018-5849-z

Nasar S, Rashid N, Iftikhar S. (2020) Dengue proteins with their role in pathogenesis, and strategies for developing an effective anti-dengue treatment: A review. Journal of Medical Virology, 92(8) doi:10.1002/jmv.25646 DOI: https://doi.org/10.1002/jmv.25646

Halstead SB. (2012) Controversies in dengue pathogenesis. Paediatrics and International Child Health, 32(SUPP1). doi:10.1179/2046904712Z.00000000045 DOI: https://doi.org/10.1179/2046904712Z.00000000045

Ministry of Health. Clinical Practice Guideline. Management of Dengue Infection in Adults Revised Second Edition. (2014) https://www.moh.gov.my/moh/attachments/5502.pdf

Muller DA, Depelsenaire ACI, Young PR. (2017) Clinical and laboratory diagnosis of dengue virus infection. Journal of Infectious Diseases, 215. doi:10.1093/infdis/jiw649 DOI: https://doi.org/10.1093/infdis/jiw649

Kikuti M. Cruz JS, Rodrigues MS, Tavares AS. Paploski IAD, Silva MMO, Santana PM, Tauro LB, Silva GAOF. Campos GS. et al. (2019) Accuracy of the SD BIOLINE Dengue Duo for rapid point-of-care diagnosis of dengue. PLoS ONE, 14(3). doi:10.1371/journal.pone.0213301 DOI: https://doi.org/10.1371/journal.pone.0213301

Krishnananthasivam S, Fernando AN, Tippalagama R, Tennekoon R. De Man J, Seneviratne D, Premawansa S, Premawansa G, De Silva AD. (2015) Evaluation of a Commercial Rapid Test Kit for Detection of Acute Dengue Infection. The Southeast Asian journal of tropical medicine and public health, 46(4).

Poloni TR, Oliveira AS, Alfonso HL, Galvo LR, Amarilla AA, Poloni DF, Figueiredo LT, V. Aquino H. (2010) Detection of dengue virus in saliva and urine by real time RT-PCR. Virology Journal, 7. doi:10.1186/1743-422X-7-22 DOI: https://doi.org/10.1186/1743-422X-7-22

Andries AC, Duong V, Ong S, Ros S, Sakuntabhai A, Horwood P, Dussart P. Buchy P. (2016) Evaluation of the performances of six commercial kits designed for dengue NS1 and anti-dengue IgM, IgG and IgA detection in urine and saliva clinical specimens. BMC Infectious Diseases, 16(1). doi:10.1186/s12879-016-1551-x DOI: https://doi.org/10.1186/s12879-016-1551-x

Andries AC, Duong V, Ly S, Cappelle J, Kim KS, Lorn TP, Ros S, Ong S, Huy R, Horwood P. et al. (2015) Value of Routine Dengue Diagnostic Tests in Urine and Saliva Specimens. PLoS Neglected Tropical Diseases, 9(9). doi:10.1371/journal.pntd.0004100 DOI: https://doi.org/10.1371/journal.pntd.0004100

Pawar R. (2015) Dengue Diagnosis: Challenges and Opportunities. Immunochemistry & Immunopathology, 1(1). doi:10.4172/2469-9756.1000105 DOI: https://doi.org/10.4172/2469-9756.1000105

Cooper R. (2017). Diagnostic and statistical manual of mental disorders (DSM). Knowledge Organization, 44(8). doi:10.5771/0943-7444-2017-8-668 DOI: https://doi.org/10.5771/0943-7444-2017-8-668

Sani MSA, Bakar J, Rahman RA, Abas F. (2020) Effects of coated capillary column, derivatization, and temperature programming on the identification of Carica papaya seed extract composition using GC/MS Analysis. Journal of Analysis and Testing, 4:23–34. doi:10.1007/s41664-020-00118-z DOI: https://doi.org/10.1007/s41664-020-00118-z

Daddiouaissa D, Amid A, Shirwan M, Sani A, and Ahmed AEM. (2021). Evaluation of metabolomics behavior of human colon cancer HT29 cell lines treated with ionic liquid graviola fruit pulp extract. Journal of Ethnopharmacology, 270:113813. doi:10.1016/j.jep.2021.113813 DOI: https://doi.org/10.1016/j.jep.2021.113813

Ismail AM, Sani MSA, Azid A, Zaki NNM, Arshad S, Tukiran NA, Abidin SASZ, Samsudin MS, Ismail A. (2021) Food forensics on gelatine source via ultra?high?performance liquid chromatography diode?array detector and principal component analysis. SN Applied Sciences, 3(79):1–19. doi:10.1007/s42452-020-04061-7 DOI: https://doi.org/10.1007/s42452-020-04061-7

Andrada MF, Vega-Hissi EG, Estrada MR, Garro Martinez JC. (2015). Application of k-means clustering, linear discriminant analysis and multivariate linear regression for the development of a predictive QSAR model on 5-lipoxygenase inhibitors. Chemometrics and Intelligent Laboratory Systems, 143:122–129. doi:10.1016/j.chemolab.2015.03.001 DOI: https://doi.org/10.1016/j.chemolab.2015.03.001

Ratner B. (2009) The correlation coefficient: Its values range between +1/?1, or do they? Journal of Targeting, Measurement and Analysis for Marketing, 17(2):139–142. doi:10.1057/jt.2009.5 DOI: https://doi.org/10.1057/jt.2009.5

Jannat B, Ghorbani K, Kouchaki S, Sadeghi N, Eslamifarsani E, Rabbani F, Beyramysoltan S. (2020) Distinguishing tissue origin of bovine gelatin in processed products using LC/MS technique in combination with chemometrics tools. Food Chemistry, 319:126302. doi:10.1016/j.foodchem.2020.126302 DOI: https://doi.org/10.1016/j.foodchem.2020.126302

Bouatra S, Aziat F, Mandal R, Guo AC, Wilson MR, Knox C, Bjorndahl TC, Krishnamurthy R, Saleem F, Liu P. et al. (2013). The Human Urine Metabolome. PLoS ONE, 8(9). doi:10.1371/journal.pone.0073076 DOI: https://doi.org/10.1371/journal.pone.0073076

Gil L, Martínez G, Tápanes R, Castro O, González D, Bernardo L, Vázquez S, Kourí G, Guzmán MG. (2004) Oxidative stress in adult dengue patients. American Journal of Tropical Medicine and Hygiene, 71(5). doi:10.4269/ajtmh.2004.71.652 DOI: https://doi.org/10.4269/ajtmh.2004.71.652

Klassen P, Biesalski HK, Mazariegos M, Solomons NW, Fürst P. (2004). Classic dengue fever affects levels of circulating antioxidants. Nutrition, 20(6). doi:10.1016/j.nut.2004.03.016 DOI: https://doi.org/10.1016/j.nut.2004.03.016

Saxena R. (2014) Arthritis as a Disease of Aging and Changes in Antioxidant Status. In: Aging: Oxidative Stress and Dietary Antioxidants, doi:10.1016/B978-0-12-405933-7.00005-6 DOI: https://doi.org/10.1016/B978-0-12-405933-7.00005-6

Smith S, Burden H, Persad R, Whittington K, De Lacy Costello B, Ratcliffe NM, Probert CS. (2008). A comparative study of the analysis of human urine headspace using gas chromatography-mass spectrometry. Journal of Breath Research, 2(3). doi:10.1088/1752-7155/2/3/037022 DOI: https://doi.org/10.1088/1752-7155/2/3/037022

Courageot MP, Catteau A, Desprès P. (2003) Mechanisms of Dengue virus-induced cell death. Advances in Virus Research, 60. doi:10.1016/S0065-3527(03)60005-9 DOI: https://doi.org/10.1016/S0065-3527(03)60005-9

Di Meo S, Reed TT, Venditti P, Victor VM. (2016) Harmful and Beneficial Role of ROS. Oxidative Medicine and Cellular Longevity, 2016: 7909186. doi:10.1155/2016/7909186 DOI: https://doi.org/10.1155/2016/7909186

Zhao F, Wang P, Lucardi RD, Su Z, Li S. (2020) Natural sources and bioactivities of 2,4-di-tert-butylphenol and its analogs. Toxins, 12(1). doi:10.3390/toxins12010035 DOI: https://doi.org/10.3390/toxins12010035

Leila A, Lamjed B, Roudaina B, Najla T, Taamalli A, Jellouli S, Mokhtar Z. (2019). Isolation of an antiviral compound from Tunisian olive twig cultivars. Microbial Pathogenesis, 128. doi:10.1016/j.micpath.2019.01.012 DOI: https://doi.org/10.1016/j.micpath.2019.01.012

Brynildsen MP, Winkler JA, Spina CS, MacDonald IC, Collins JJ. (2013). Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production. Nature Biotechnology, 31(2). doi:10.1038/nbt.2458 DOI: https://doi.org/10.1038/nbt.2458