Papers by Shamala Devi Sekaran
Rapid Reviews Infectious Diseases Reviews of "Identifying the Role of Household Immunity in Drivi... more Rapid Reviews Infectious Diseases Reviews of "Identifying the Role of Household Immunity in Driving Individual Dengue Virus Infection Risk 2 To read the original manuscript, click the link above. Reviewer 1 (Shamala Devi S…) | ◻ To read the reviews, click the links below.
Frontiers in Cellular and Infection Microbiology
TheFlavivirusgenus is made up of viruses that are either mosquito-borne or tick-borne and other v... more TheFlavivirusgenus is made up of viruses that are either mosquito-borne or tick-borne and other viruses transmitted by unknown vectors. Flaviviruses present a significant threat to global health and infect up to 400 million of people annually. As the climate continues to change throughout the world, these viruses have become prominent infections, with increasing number of infections being detected beyond tropical borders. These include dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV). Several highly conserved epitopes of flaviviruses had been identified and reported to interact with antibodies, which lead to cross-reactivity results. The major interest of this review paper is mainly focused on the serological cross-reactivity between DENV serotypes, ZIKV, WNV, and JEV. Direct and molecular techniques are required in the diagnosis ofFlavivirus-associated human disease. In this review, the serological assays such as neutralization te...
Frontiers in Cellular and Infection Microbiology
Dengue is a major public health concern, affecting almost 400 million people worldwide, with abou... more Dengue is a major public health concern, affecting almost 400 million people worldwide, with about 70% of the global burden of disease in Asia. Despite revised clinical classifications of dengue infections by the World Health Organization, the wide spectrum of the manifestations of dengue illness continues to pose challenges in diagnosis and patient management for clinicians. When the Zika epidemic spread through the American continent and then later to Africa and Asia in 2015, researchers compared the characteristics of the Zika infection to Dengue, considering both these viruses were transmitted primarily through the same vector, the Aedes aegypti female mosquitoes. An important difference to note, however, was that the Zika epidemic diffused in a shorter time span compared to the persisting feature of Dengue infections, which is endemic in many Asian countries. As the pathogenesis of viral illnesses is affected by host immune responses, various immune modulators have been propose...
Additional file 2: Figure S1. (A) Plasma levels IL-18BPa and free circulating IL-18 in dengue pat... more Additional file 2: Figure S1. (A) Plasma levels IL-18BPa and free circulating IL-18 in dengue patients at febrile and defeverscence phase. (B) Spearman correlation between IL-18 and IL-18BP among DWS and DWS+/SD. Levels of biomarkers were compared across the three patient groups and post hoc Mann–Whitney U tests were then performed for those biomarkers with a Kruskal–Wallis test P value of <0.05. A Spearman rank test was used to compare the correlation between two continuous variables. ****P
Conserved non-synonymous single nucleotide polymorphisms (SNPs) associated with penicillin bindin... more Conserved non-synonymous single nucleotide polymorphisms (SNPs) associated with penicillin binding proteins (PBPs) and other virulent genes found in resistant isolates. (DOCX 29Â kb)
Full list of non-synonymous single nucleotide polymorphisms (SNPs) in all ten pneumococcal clinic... more Full list of non-synonymous single nucleotide polymorphisms (SNPs) in all ten pneumococcal clinical isolates. (XLSX 8827Â kb)
Assembly and gene content of all the ten pneumococcal clinical isolates. (XLSX 288Â kb)
The Southeast Asian journal of tropical medicine and public health, 1987
A modification of the IgM-capture ELISA which can provide an early diagnosis for dengue infection... more A modification of the IgM-capture ELISA which can provide an early diagnosis for dengue infection is presented. The test is technically simple compared to HI and appears to be more sensitive. It has the advantage over HIT for the detection of specific IgM in that it is more sensitive and the reading of the result is not subjective. There is the possibility of the test being able to replace HI and HIT in the future.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 2009
Dengue infection is a major public health problem affecting millions of people living in tropical... more Dengue infection is a major public health problem affecting millions of people living in tropical countries. With no suitable vaccines and specific antiviral drugs, treatment for dengue is usually symptomatic and supportive. Early diagnosis and recognition of severe disease is therefore crucial for better management of the patient. Two-dimension electrophoresis was used to identify disease-associated proteins that can be used for diagnosis and as drug targets for treatment. Two markers, identified by mass spectrometry analysis as alpha1-antitrypsin and NS1 proteins were found to be upregulated in dengue fever (DF; n=10) and dengue haemorrhagic fever (DHF; n=10) patients compared with healthy individuals (n=8). Both alpha1-antitrypsin and NS1 proteins were overexpressed two-fold in DHF patients compared with DF patients. Our study suggests that alpha1-antitrypsin and NS1 protein could be used as biomarkers as early indicators of DHF risk among patients with suspected dengue infection.
Journal of Virological Methods, 2007
Tioman virus is a newly described bat-urine derived paramyxovirus isolated in Tioman Island, Mala... more Tioman virus is a newly described bat-urine derived paramyxovirus isolated in Tioman Island, Malaysia in 2001. Hitherto, neither human nor animal infection by this virus has been reported. Nonetheless, its close relationship to another paramyxovirus, the Menangle virus which had caused diseases in humans and pigs [
Journal of Virological Methods, 2006
The use of the polymerase chain reaction (PCR) in molecular diagnosis is now accepted worldwide a... more The use of the polymerase chain reaction (PCR) in molecular diagnosis is now accepted worldwide and has become an essential tool in the research laboratory. In the laboratory, a rapid detection, serotyping and quantitation, one-step real-time RT-PCR assay was developed for dengue virus using TaqMan probes. In this assay, a set of forward and reverse primers were designed targeting the serotype conserved region at the NS5 gene, at the same time flanking a variable region for all four serotypes which were used to design the serotype-specific TaqMan probes. This multiplex one-step RT-PCR assay was evaluated using 376 samples collected during the year 2003. These groups included RNA from prototype dengue virus (1-4), RNA from acute serum from which dengue virus was isolated, RNA from tissue culture supernatants of dengue virus isolated, RNA from seronegative acute samples (which were culture and IgM negative) and RNA from samples of dengue IgM positive sera. The specificity of this assay was also evaluated using a panel of sera which were positive for other common tropical disease agents including herpes simplex virus, cytomegalovirus, measles virus, varicella-zoster virus, rubella virus, mumps virus, WWF,
Genomics Data, 2015
Cobalt (Co 2+) is an important transition metal ion that plays a vital role in cellular physiolog... more Cobalt (Co 2+) is an important transition metal ion that plays a vital role in cellular physiology of bacteria. The role of Co 2+ in the regulation of several genes/operons in Streptococcus pneumoniae has recently been reported [1]. The data described in this article relate to the genome-wide transcriptional profiling of Streptococcus pneumoniae D39, either in the presence or absence of 0.5 mM Co 2+ in chemically defined medium (CDM) using DNA microarray analysis. Genes belonging to a broad range of cellular processes such as virulence, transport and efflux systems, stress response and surface attachment were differentially expressed in the presence of Co 2+. We used transcriptional lacZ assays and electrophoretic mobility shift assays (EMSAs) to confirm our results [1]. The dataset is publicly available at the Gene Expression Omnibus (GEO) repository (http://www.ncbi.nlm.nih.gov/ geo/) with accession number GSE57696.
The Journal of Immunology
Dengue has neither licensed drugs nor vaccines and Its immunopathogenesis is elusive. The disease... more Dengue has neither licensed drugs nor vaccines and Its immunopathogenesis is elusive. The disease is widespread and imposes healthcare, economic and social burden on endemic countries like Malaysia. This study aims to understand and identify clinical and immunological markers of disease. Dengue suspected patients were recruited in 2 hospitals where 77% of the study population was categorized as dengue with warning signs. Diagnosis based solely on clinical symptoms is insufficient. Clinically, platelet counts of dengue patients were low and together with increased vWF and prolonged clotting time, retain thrombocytopenia in dengue as an excellent marker for disease progression but not as a differentiator for patients with and without warning signs. Liver enzymes, ALT and AST, were good indicators for dengue disease progression. Immunogenetically, HLA alleles A*24 and B*57 and A*03 were associated with Chinese, Indians and Malay dengue patients, respectively. Three non-structural prote...
Biosensors
Dengue is a major threat to public health globally. While point-of-care diagnosis of acute/recent... more Dengue is a major threat to public health globally. While point-of-care diagnosis of acute/recent dengue is available to reduce its mortality, a lack of rapid and accurate testing for the detection of previous dengue remains a hurdle in expanding dengue seroepidemiological surveys to inform its prevention, especially vaccination, to reduce dengue morbidity. This study evaluated ViroTrack Dengue Serostate, a biosensors-based semi-quantitative anti-dengue IgG (immunoglobulin G) immuno-magnetic agglutination assay for the diagnosis of previous and recent dengue in a single test. Blood samples were obtained from 484 healthy participants recruited randomly from two communities in Petaling district, Selangor, Malaysia. The reference tests were Panbio Dengue IgG indirect and capture enzyme-linked immunosorbent assays, in-house hemagglutination inhibition assay, and focus reduction neutralization test. Dengue Serostate had a sensitivity and specificity of 91.1% (95%CI 87.8–93.8) and 91.1% (...
Prime Archives in Biomedical Sciencesy, 2020
Streptococcus pneumoniae is the leading cause of respiratory infections worldwide, specifically c... more Streptococcus pneumoniae is the leading cause of respiratory infections worldwide, specifically community-acquired pneumonia. Due to the overuse of antibiotics, S. pneumoniae has developed a high degree of resistance to a wide range of antibacterial drugs. In this study, we performed whole genome sequencing (WGS) for ten pneumococcal clinical isolates with different levels of antibiotic resistance. The key objective is to investigate genetic changes associated with antibiotic resistance in S. pneumoniae. Our results showed that resistant isolates Prime Archives in Biomedical Sciences 3 www.videleaf.com contain higher non-synonymous single nucleotide polymorphisms (SNPs) within genes coding for virulence factors as compared to susceptible isolates, suggesting that drug resistance is essentially determined by the occurrence of SNPs rather than the presence or absence of virulent genes. In addition, 90 SNPs were identified that were unique to resistant isolates. Out of these 90 SNPs, 31 were unique and have not been reported previously. Detection of SNPs associated with antibiotic resistance is crucial for the future use of genome sequencing to predict antibiotic susceptibility in clinical microbiology and for developing new anti-pneumococcal drugs.
Zika Virus Biology, Transmission, and Pathology, 2021
Abstract The blood brain barrier is a complex network of junctions that preserves homeostasis of ... more Abstract The blood brain barrier is a complex network of junctions that preserves homeostasis of the central nervous system and confines diffusion of soluble molecules and immune cells from the systemic compartments of the body into the central nervous system. Unfortunately, the blood brain barrier is not impenetrable as evidenced by the multitude of viruses or other pathological circumstances that either lead to damage or breakdown of these junctional proteins. As a neurotropic flavivirus, Zika virus infection leads to neurological disorders such as Guillain-Barre syndrome in adults, it also causes congenital malformations such as microcephaly, calcifications of the central nervous system and ventriculomegaly in newborns through transplacental transmission from infected mothers to fetus during pregnancy. Disruption of the blood brain barrier is the event that occurs prior to viral entry into the central nervous system, causing impairment of fetal and maternal cells including neural stem cells, astrocytes, neural progenitor cells, microglia, Hofbauer cells, and endothelial cells. Endothelial dysfunction is normally identified as the cause of integrity disruption of blood brain barrier by flaviviruses and it has been reported that ZIKV penetration disrupt endothelial integrity, thus, compromising the blood brain barrier. This review discusses the mechanisms exploited by Zika virus for viral entry and crossing the blood brain barrier, as well as endothelial dysfunction reported in different flavivirus infections.
PLOS ONE, 2020
Severe dengue can be lethal caused by manifestations such as severe bleeding, fluid accumulation ... more Severe dengue can be lethal caused by manifestations such as severe bleeding, fluid accumulation and organ impairment. This study aimed to investigate the role of dengue non-structural 1 (NS1) protein and host factors contributing to severe dengue. Electrical cell-substrate impedance sensing system was used to investigate the changes in barrier function of microvascular endothelial cells treated NS1 protein and serum samples from patients with different disease severity. Cytokines and metabolites profiles were assessed using a multiplex cytokine assay and liquid chromatography mass spectrometry respectively. The findings showed that NS1 was able to induce the loss of barrier function in microvascular endothelium in a dose dependent manner, however, the level of NS1 in serum samples did not correlate with the extent of vascular leakage induced. Further assessment of host factors revealed that cytokines such as CCL2, CCL5, CCL20 and CXCL1, as well as adhesion molecule ICAM-1, that are involved in leukocytes infiltration were expressed higher in dengue patients in comparison to healthy individuals. In addition, metabolomics study revealed the presence of deregulated metabolites involved in the phospholipid metabolism pathway in patients with severe manifestations. In conclusion, disease severity in dengue virus infection did not correlate directly with NS1 level, but instead with host factors that are involved in the regulation of junctional integrity and phospholipid metabolism. However, as the studied population was relatively small in this study, these exploratory findings should be confirmed by expanding the sample size using an independent cohort to further establish the significance of this study.
Medicine, 2018
Dengue virus is one of the most widespread flaviviruses that re-emerged throughout recent decades... more Dengue virus is one of the most widespread flaviviruses that re-emerged throughout recent decades. The progression from mild dengue to severe dengue (SD) with the complications such as vascular leakage and hemorrhage increases the fatality rate of dengue. The pathophysiology of SD is not entirely clear. To investigate potential biomarkers that are suggestive of pathogenesis of SD, a small panel of serum samples selected from 1 healthy individual, 2 dengue patients without warning signs (DWSÀ), 2 dengue patients with warning signs (DWS+), and 5 patients with SD were subjected to a pilot analysis using Sengenics Immunome protein array. The overall fold changes of protein expressions and clustering heat map revealed that PFKFB4, TPM1, PDCL3, and PTPN20A were elevated among patients with SD. Differential expression analysis identified that 29 proteins were differentially elevated greater than 2fold in SD groups than DWSÀ and DWS+. From the 29 candidate proteins, pathways enrichment analysis also identified insulin signaling and cytoskeleton pathways were involved in SD, suggesting that the insulin pathway may play a pivotal role in the pathogenesis of SD. Abbreviations: AFF4 = AF4/FMR2 Family Member 4, BCCP = biotin carboxyl carrier protein, COPS6 = COP9 Signalosome Subunit 6, CV = coefficient of variant, Cy3BSA = Cy3 labelled bovine serum albumin, DAMPs = damage-associated molecular patterns, DENV = dengue virus, DWSÀ = dengue patients without warning signs, DWSÀ = dengue warning signs negative (dengue with warning signs), DWS+ = dengue patients with warning signs, DWS+ = dengue warning signs positive (dengue without warning signs), ELISA = enzyme-linked immunosorbent assay, FC = fold change, HC = healthy control, HI = hemagglutination inhibition, KRT19 = Keratin 19, NS1 = nonstructural protein 1, PCR = polymerase chain reaction, PDCL3 = phosducin like 3, PFKFB4 = 6phosphofructo-2-kinase/ fructose-2 =6-biphosphatase 4, PTPN20A = protein tyrosine phosphatase; nonreceptor type 20A, RFU = relative fluorescence unit, SAB = serum assay buffer, SD = patients with severe dengue, SD = severe dengue, TP53 = tumor protein p53, TPM1 = tropomyosin-alpha 1, VIAF = viral IAP-associated factor 1.
Sensors and Actuators B: Chemical, 2018
In this review, we describe the existing diagnostic tests, rapid diagnostic tests, and emerging p... more In this review, we describe the existing diagnostic tests, rapid diagnostic tests, and emerging pointof-care diagnostic assays for diseases caused by dengue virus (DENV). We organize these recently 2 reported diagnostic technologies by the type of detection platform. First, fabrication of the platform of several modules used for detection of DENV biomarkers is explained. This section is followed by an assessment of the advantages, disadvantages, and limitations of the different diagnostic procedures. Finally, our views regarding the future perspectives in this area are presented.
Journal of Food and Drug Analysis, 2016
Chemotherapies remain far from ideal due to drug resistance; therefore, novel chemotherapeutic ag... more Chemotherapies remain far from ideal due to drug resistance; therefore, novel chemotherapeutic agents with higher effectiveness are crucial. The extracts of four Phyllanthus species, namely Phyllanthus niruri, Phyllanthus urinaria, Phyllanthus watsonii, and Phyllanthus amarus, were shown to induce apoptosis and inhibit metastasis of breast carcinoma cells (MCF-7). The main objective of this study was to determine the pathways utilized by these four Phyllanthus species to exert anti-metastatic activities. A cancer 10-pathway reporter was used to investigate the pathways affected by the four Phyllanthus species. Results indicated that these Phyllanthus species suppressed breast carcinoma metastasis and proliferation by suppressing matrix metalloprotein 2 and 9 expression via inhibition of the extracellular signal-related kinase (ERK) pathway. Additionally, inhibition of hypoxiainducible factor 1-a in the hypoxia pathway caused reduced vascular endothelial growth factor and inducible nitric oxide synthase expression, resulting in anti-angiogenic effects and eventually anti-metastasis. Two-dimensional gel electrophoresis identified numerous proteins suppressed by these Phyllanthus species, including invasion proteins, antiapoptotic protein, protein-synthesis proteins, angiogenic and mobility proteins, and various glycolytic enzymes. Our results indicated that ERK and hypoxia pathways are the most likely targets of the four Phyllanthus species for the inhibition of MCF-7 metastasis.
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Papers by Shamala Devi Sekaran