ORCID Profile
0000-0001-9975-3165
Current Organisation
Australian Institute of Tropical Health and Medicine
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Publisher: American Association for Cancer Research (AACR)
Date: 05-2023
DOI: 10.1158/1055-9965.22724993.V1
Abstract: Supplementary Table S3 shows positivity rates of the 46 in idual markers among cases and controls in each study
Publisher: MDPI AG
Date: 13-09-2022
Abstract: Whole-blood-derived transcriptional profiling is widely used in biomarker discovery, immunological research, and therapeutic development. Traditional molecular and high-throughput transcriptomic platforms, including molecular assays with quantitative PCR (qPCR) and RNA-sequencing (RNA-seq), are dependent upon high-quality and intact RNA. However, collecting high-quality RNA from field studies in remote tropical locations can be challenging due to resource restrictions and logistics of post-collection processing. The current study tested the relative performance of the two most widely used whole-blood RNA collection systems, PAXgene® and Tempus™, in optimal laboratory conditions as well as suboptimal conditions in tropical field sites, including the effects of extended storage times and high storage temperatures. We found that Tempus™ tubes maintained a slightly higher RNA quantity and integrity relative to PAXgene® tubes at suboptimal tropical conditions. Both PAXgene® and Tempus™ tubes gave similar RNA purity (A260/A280). Additionally, Tempus™ tubes preferentially maintained the stability of mRNA transcripts for two reference genes tested, Succinate dehydrogenase complex, subunit A (SDHA) and TATA-box-binding protein (TBP), even when RNA quality decreased with storage length and temperature. Both tube types preserved the rRNA transcript 18S ribosomal RNA (18S) equally. Our results suggest that Tempus™ blood RNA collection tubes are preferable to PAXgene® for whole-blood collection in suboptimal tropical conditions for RNA-based studies in resource-limited settings.
Publisher: Springer Science and Business Media LLC
Date: 17-11-2020
Publisher: American Association for Cancer Research (AACR)
Date: 14-02-2023
DOI: 10.1158/1055-9965.EPI-22-0452
Abstract: Epstein–Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL). Anti-EBV IgG and IgA antibody responses targeting 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case–control studies investigating EBV-positive cHL, eBL, NPC, and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life-cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their association with each cancer type. In an additional analysis, we focused on the subset of 46 in idual antibodies representing the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models. IgA antibody responses targeting all EBV life-cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle cHL with antibodies in the early lytic, late lytic and glycoprotein stages and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types. Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis. Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer.
Publisher: MDPI AG
Date: 31-07-2019
DOI: 10.3390/V11080700
Abstract: Chronic kidney disease of unknown etiology (CKDu) imposes a substantial burden on public health in Sri Lankan agricultural communities. High seroprevalences of hantavirus have been reported in CKDu patients in several locations of Sri Lanka. We carried out a cross-sectional study followed by an unmatched case-control comparison in two geographically distinct areas of Sri Lanka, Girandurukotte (CKDu endemic) and Kandy (CKDu non-endemic) to determine whether exposure to hantaviruses is a potential risk factor in patients with kidney disease. An indirect immunofluorescent antibody assay using two antigens, Thailand orthohantavirus-infected and recombinant N protein-expressing Vero E6 cells, were used for serodiagnosis. Participants’ demographic and other socio-economic data were collected through a structured questionnaire. Fifty kidney disease patients and 270 controls from Kandy and 104 kidney disease patients and 242 controls from Girandurukotte were examined. Seropositivities were 50% and 17.4% in kidney patients and controls, respectively, in Girandurukotte, and they were 18% and 7% in Kandy. The odds of exposure to hantaviruses were higher for kidney disease patients than for controls in both Girandurukotte (OR:3.66, 95% CI:2.01 to 6.64) and Kandy (OR:2.64, 95% CI:1.07 to 6.54) in binary logistic regression models. According to statistical analysis, in iduals exposed to hantaviruses had a higher risk of developing renal impairment. Therefore, hantavirus infection might be an important risk factor for development of kidney disease in Sri Lanka.
Publisher: Elsevier BV
Date: 04-2017
Publisher: Cold Spring Harbor Laboratory
Date: 06-2023
DOI: 10.1101/2023.05.31.23290784
Abstract: Chronic kidney disease (CKD) and chronic kidney disease of uncertain etiology (CKDu) are chronic renal diseases that pose a significant health burden in Sri Lanka. Leptospirosis is a bacterial zoonosis that primarily damages kidney tissues via colonization of Leptospira spp. in the renal tubules and is a suspected etiological agent of CKDu. Since Sri Lanka is a leptospirosis endemic country where outbreaks of the disease have been reported, this study aimed to find the association between leptospirosis and chronic renal disease in two geographically distinct regions of Sri Lanka, Kandy (CKDu non-endemic) and Badulla (CKDu endemic) districts. Forty-nine chronic renal disease patients and 135 controls from Kandy and 89 chronic renal disease patients and 149 controls from Badulla were examined serologically by microscopic agglutination test with a panel of 11 Leptospira serogroups. A seroprevalence of 35.3% and 32.5% for leptospirosis was observed in the Girandurukotte CKDu group and Girandurukotte control group respectively, while a seroprevalence of 36.7% and 31.9% were observed in the Kandy CKDu group and Kandy control group respectively. No statistically significant differences in leptospirosis seropositivity were observed between the chronic renal disease and control groups in both districts. However, further longitudinal studies assessing renal colonization among chronic renal patients and healthy in iduals are required to conclusively state whether leptospirosis plays an important role in chronic renal disease development and/or progression in Sri Lanka.
Publisher: Mary Ann Liebert Inc
Date: 11-2019
Abstract: We have reported high seroprevalence to Thailand orthohantavirus (THAIV) or THAIV-related orthohantavirus (TRHV) among patients with chronic kidney disease of unknown etiology in Girandurukotte, Sri Lanka. THAIV or TRHV infection is considered to be transmitted by rodent hosts in this area, but its reservoir rodents have not yet been identified. Hence, 116 rodents were captured, and seroprevalences were examined by indirect immunofluorescent antibody assay (immunofluorescence assay [IFA]) using antigens of THAIV strain Thai749-infected Vero E6 cells and recombinant nucleocapsid protein of THAIV expressed in Vero E6 cell. Molecular biological species identification of rodents was carried out by sequencing
Publisher: Springer Science and Business Media LLC
Date: 08-12-2021
DOI: 10.1038/S41598-021-02788-W
Abstract: Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy that has been etiologically linked to Epstein-Barr virus (EBV) infection, with EBV gene transcripts identified in almost all cases. However, the humoral immune response to EBV in NKTCL patients has not been well characterized. We examined the antibody response to EBV in plasma s les from 51 NKTCL cases and 154 controls from Hong Kong and Taiwan who were part of the multi-center, hospital-based AsiaLymph case–control study. The EBV-directed serological response was characterized using a protein microarray that measured IgG and IgA antibodies against 202 protein sequences representing the entire EBV proteome. We analyzed 157 IgG antibodies and 127 IgA antibodies that fulfilled quality control requirements. Associations between EBV serology and NKTCL status were disproportionately observed for IgG rather than IgA antibodies. Nine anti-EBV IgG responses were significantly elevated in NKTCL cases compared with controls and had ORs highest vs. lowest tertile 6.0 (Bonferroni-corrected P -values 0.05). Among these nine elevated IgG responses in NKTCL patients, three IgG antibodies (all targeting EBNA3A) are novel and have not been observed for other EBV-associated tumors of B-cell or epithelial origin. IgG antibodies against EBNA1, which have consistently been elevated in other EBV-associated tumors, were not elevated in NKTCL cases. We characterize the antibody response against EBV for patients with NKTCL and identify IgG antibody responses against six distinct EBV proteins. Our findings suggest distinct serologic patterns of this NK/T-cell lymphoma compared with other EBV-associated tumors of B-cell or epithelial origin.
Publisher: American Association for Cancer Research (AACR)
Date: 05-2023
DOI: 10.1158/1055-9965.22725002.V1
Abstract: Supplementary Methods S1 expands upon data and statistical methods.
Publisher: Springer Science and Business Media LLC
Date: 04-10-2019
DOI: 10.1007/S00705-018-4053-X
Abstract: Chronic kidney disease of unknown aetiology (CKDu) reported in Sri Lanka and other countries is a mysterious and serious disease. Recently, we reported a high seroprevalence of antibodies to a hantavirus antigen among CKDu patients in Girandurukotte, Badulla district, Sri Lanka. However, the type of hantavirus with which the residents were infected was not determined. In this study, a total of 89 seropositive sera were examined to identify their serotypes using an indirect immunofluorescent antibody assay, a truncated-N-protein-based enzyme-linked immunosorbent assay, and a cross-neutralization test. These results indicated that the residents in this area were frequently infected with Thailand orthohantavirus or an antigenically related virus.
Publisher: MDPI AG
Date: 11-12-2019
DOI: 10.3390/V11121150
Abstract: Dear Drs. W. Katherine Yih, Martin Kulldorff, Jessica H. Leibler, David J. Friedman, and Daniel R. Brooks [...]
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.MEHY.2016.04.009
Abstract: Chronic kidney disease of uncertain etiology (CKDu) has been a severe burden and a public health crisis in Sri Lanka over the past two decades. Many studies have established hypotheses to identify potential risk factors although causative agents, risk factors and etiology of this disease are still uncertain. Several studies have postulated that fungal and bacterial nephrotoxins are a possible etiological factor however, the precise link between hypothesized risk factors and the pathogenesis of chronic kidney disease has yet to be proven in prior studies. Leptospirosis and Hantavirus infections are important zoonotic diseases that are naturally maintained and transmitted via infected rodent populations and which present similar clinical and epidemiological features. Both infections are known to be a cause of acute kidney damage that can proceed into chronic renal failure. Several studies have reported presence of both infections in Sri Lanka. Therefore, we hypothesized that pathogenic Leptospira or Hantavirus are possible causative agents of acute kidney damage which eventually progresses to chronic kidney disease in Sri Lanka. The proposed hypothesis will be evaluated by means of an observational study design. Past infection will be assessed by a cross-sectional study to detect the presence of IgG antibodies with further confirmatory testing among chronic kidney disease patients and in iduals from the community in selected endemic areas compared to low prevalence areas. Identification of possible risk factors for these infections will be followed by a case-control study and causality will be further determined with a cohort study. If the current hypothesis is true, affected communities will be subjected for medical interventions related to the disease for patient management while considering supportive therapies. Furthermore and possibly enhance their preventive and control measures to improve vector control to decrease the risk of infection.
Publisher: American Association for Cancer Research (AACR)
Date: 05-2023
DOI: 10.1158/1055-9965.22725002
Abstract: Supplementary Methods S1 expands upon data and statistical methods.
Publisher: American Association for Cancer Research (AACR)
Date: 05-2023
DOI: 10.1158/1055-9965.22724993
Abstract: Supplementary Table S3 shows positivity rates of the 46 in idual markers among cases and controls in each study
Publisher: American Association for Cancer Research (AACR)
Date: 05-2023
DOI: 10.1158/1055-9965.C.6624590.V1
Abstract: AbstractBackground: Epstein–Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL). Methods: Anti-EBV IgG and IgA antibody responses targeting 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case–control studies investigating EBV-positive cHL, eBL, NPC, and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life-cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their association with each cancer type. In an additional analysis, we focused on the subset of 46 in idual antibodies representing the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models. Results: IgA antibody responses targeting all EBV life-cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle cHL with antibodies in the early lytic, late lytic and glycoprotein stages and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types. Conclusions: Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis. Impact: Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer. /
Publisher: American Association for Cancer Research (AACR)
Date: 05-2023
DOI: 10.1158/1055-9965.22724996
Abstract: Supplementary Table S2 shows summary of participant characteristics
Publisher: American Association for Cancer Research (AACR)
Date: 05-2023
DOI: 10.1158/1055-9965.22724996.V1
Abstract: Supplementary Table S2 shows summary of participant characteristics
Publisher: MDPI AG
Date: 02-10-2021
DOI: 10.3390/V13101984
Abstract: We reported the genetic evidence of circulating hantaviruses from small mammals captured in a chronic kidney disease of unknown etiology (CKDu) hotspot area of Sri Lanka. The high seroprevalence of anti-hantavirus antibodies against Thailand orthohantavirus (THAIV) has been reported among CKDu patients and rodents in Sri Lankan CKDu hotspots. We captured 116 small mammals from CKDu endemic regions in the Polonnaruwa District of Sri Lanka. Seven animals (five out of 11 Mus booduga and two out of 99 Rattus rattus) were PCR-positive for the hantavirus. A rat-borne sequence was grouped with a THAIV-like Anjozorobe virus. In contrast, Mus-borne sequences belonged to the THAIV lineage, suggesting a novel orthohantavirus species according to the phylogenetic analyses and whole-genome comparisons. Our genetic evidence indicates the presence of two THAIV-related viruses circulating in this CKDu endemic area, suggesting a basis for further investigations to identify the infectious virus in patients with CKDu and the CKDu induction mechanism of these viruses.
Publisher: American Association for Cancer Research (AACR)
Date: 05-2023
DOI: 10.1158/1055-9965.C.6624590
Abstract: AbstractBackground: Epstein–Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL). Methods: Anti-EBV IgG and IgA antibody responses targeting 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case–control studies investigating EBV-positive cHL, eBL, NPC, and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life-cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their association with each cancer type. In an additional analysis, we focused on the subset of 46 in idual antibodies representing the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models. Results: IgA antibody responses targeting all EBV life-cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle cHL with antibodies in the early lytic, late lytic and glycoprotein stages and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types. Conclusions: Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis. Impact: Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer. /
Publisher: American Association for Cancer Research (AACR)
Date: 05-2023
DOI: 10.1158/1055-9965.22724999
Abstract: Supplementary Table S1 shows marker pathway allocation and corresponding citations
Publisher: American Association for Cancer Research (AACR)
Date: 05-2023
DOI: 10.1158/1055-9965.22724999.V1
Abstract: Supplementary Table S1 shows marker pathway allocation and corresponding citations
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Yomani Dilukshi Sarathkumara.