Publications by authors named "Ketheesan N"

Post-streptococcal glomerulonephritis (PSGN) is primarily associated with preceding group A streptococcal skin or throat infections, now mainly observed in economically disadvantaged communities. This condition significantly predisposes individuals to later-life chronic kidney disease and concurrent renal complications, with the elderly experiencing increased severity and less favourable outcomes. Streptococcal pyrogenic exotoxin B and nephritis-associated plasmin receptor are identified nephritogenic antigens (nephritogens).

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Travel restrictions, pandemics, economic downturn, and increasing costs in organizing workshops all impact on face-to-face training of undergraduates planning to undertake research. The inability to obtain basic, first-hand information regarding research in practice causes undue stress for students and leads to unrealistic expectations regarding research projects. Here, we describe how a student initiated online workshop, co-designed by a group of undergraduate leaders in conjunction with a panel of international academic researchers, and enabled the delivery of an introductory workshop on research training to meet student needs.

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Article Synopsis
  • Q fever is a disease caused by a bacterium that poses risks to people working in animal-related jobs and those in contact with wildlife.
  • While many people experience no symptoms, about 5% of those who do can develop serious long-term health issues, such as endocarditis.
  • The review discusses how the immune response to Q fever can influence disease outcomes and highlights ongoing efforts to develop a safer, cost-effective vaccine, as the current vaccine (Q-VAX) can cause adverse reactions in those previously exposed.
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The online education market share is rapidly increasing, raising the demand to teach sciences outside the laboratory environment. Here, we present Microbiology at Home (M@H), a new approach that integrates hands-on microbiology experimentation with online interactive simulations using authentic scenarios in microbiology in the home environment. The M@H program includes 8 practical activities aligned to the ASM curriculum for practical skills.

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Introduction: The present study evaluated the characteristics of the initial dengue outbreaks in the Jaffna peninsula, a region without dengue prior to mid-2009 in dengue-endemic Sri Lanka, a tropical island nation.

Methodology: This is a cross-sectional study conducted using a total of 765 dengue patients' clinical data and samples collected from the Teaching Hospital, Jaffna during the initial dengue outbreaks. Clinical, non-specific, and specific virological laboratory characteristics including the platelet count, NS1 antigen, and anti-DENV IgM/IgG were evaluated as correlates of dengue virus (DENV) infection in the two initial outbreaks of 2009/2010 and 2011/2012 in Northern Sri Lanka.

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We have developed a candidate vaccine to protect against multiple strains of Streptococcus pyogenes infections. The candidate vaccine contains two synthetic peptides derived from S. pyogenes proteins: the M-protein epitope, p*17 and the IL-8 degrading S.

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Melioidosis is a neglected tropical disease that causes high morbidity and mortality. Public health awareness is essential for both prevention and early detection of the infection. This project aimed to develop an internationally applicable educational tool to increase community awareness in regions with high prevalence of diabetes and melioidosis.

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Objective: To assess awareness and risk of Q fever among agricultural show attendees.

Setting: University of New England's Farm of the Future Pavilion, 2019, Sydney Royal Agricultural Show.

Participants: Participants were ≥18 years, fluent in English, Australian residents, and gave their informed consent.

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  • Group A streptococcal (GAS) infections can trigger autoimmune diseases like acute rheumatic fever (ARF) and rheumatic heart disease (RHD), as antibodies against GAS M proteins mistakenly target heart and brain tissues.
  • The study suggests that Streptococcus dysgalactiae subspecies equisimilis (SDSE), which also has M proteins similar to GAS, might contribute to ARF/RHD and related neurobehavioral issues.
  • Experiments on Lewis rats showed that exposure to GAS and SDSE M proteins led to significant heart and behavior changes, supporting the idea that various streptococci can cause autoimmune reactions linked to these diseases.
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Host immunity plays a central role in the regulation of anti-tumour responses during checkpoint inhibitor therapy (CIT). The mechanisms involved in long lasting remission remain unclear. Animal studies have revealed that the microbiome influences the host immune response.

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Tuberculosis (TB) is one of the deadliest infectious diseases in the world. The metabolic disease type 2 diabetes (T2D) significantly increases the risk of developing active TB. Effective new TB vaccine candidates and novel therapeutic interventions are required to meet the challenges of global TB eradication.

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Background: The neuropsychiatric disorders due to post-streptococcal autoimmune complications such as Sydenham's chorea (SC) are associated with acute rheumatic fever and rheumatic heart disease (ARF/RHD). An animal model that exhibits characteristics of both cardiac and neurobehavioral defects in ARF/RHD would be an important adjunct for future studies. Since age, gender, strain differences, and genotypes impact on the development of autoimmunity, we investigated the behavior of male and female Wistar and Lewis rat strains in two age cohorts (<6 weeks and >12 weeks) under normal husbandry conditions and following exposure to group A streptococcus (GAS).

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Current diagnosis of Acute Rheumatic Fever and Rheumatic Heart Disease (ARF/RHD) relies on a battery of clinical observations aided by technologically advanced diagnostic tools and non-specific laboratory tests. The laboratory-based assays fall into two categories: those that (1) detect "evidence of preceding streptococcal infections" (ASOT, anti-DNAse B, isolation of the Group A from a throat swab) and (2) those that detect an ongoing inflammatory process (ESR and CRP). These laboratory tests are positive during any streptococcal infection and are non-specific for the diagnosis of ARF/RHD.

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The pathogenesis of Acute Rheumatic Fever/Rheumatic Heart Disease (ARF/RHD) and associated neurobehavioral complications including Sydenham's chorea (SC) is complex. Disease complications triggered by Group A streptococcal (GAS) infection are confined to human and determining the early events leading to pathology requires a robust animal model that reflects the hallmark features of the disease. However, modeling these conditions in a laboratory animal, of a uniquely human disease is challenging.

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Group A streptococci can trigger autoimmune responses that lead to acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Some autoantibodies generated in ARF/RHD target antigens in the S2 subfragment region of cardiac myosin. However, little is known about the kinetics of these antibodies during the disease process.

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Prokaryotic cell transcriptomics has been limited to mixed or sub-population dynamics and individual cells within heterogeneous populations, which has hampered further understanding of spatiotemporal and stage-specific processes of prokaryotic cells within complex environments. Here we develop a 'TRANSITomic' approach to profile transcriptomes of single Burkholderia pseudomallei cells as they transit through host cell infection at defined stages, yielding pathophysiological insights. We find that B.

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Co-occurrence of bacterial infections with type 2 diabetes (T2D) is a global problem. Melioidosis caused by Burkholderia pseudomallei is 10 times more likely to occur in patients with T2D, than in normoglycemic individuals. Using an experimental model of T2D, we observed that greater susceptibility in T2D was due to differences in proportions of infiltrating leucocytes and reduced levels of MCP-1, IFN-γ and IL-12 at sites of infection within 24 h post-infection.

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Cancer immunotherapy with checkpoint blockade has become standard of care treatment for numerous cancer types. Despite this, robust predictive biomarkers are lacking. There is increasing evidence that the host microbiome is a predictor of immunotherapy response, although the optimal host microbiome has not been defined.

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Comorbid type 2 diabetes poses a great challenge to the global control of tuberculosis. Here, we assessed the efficacy of metformin (MET), an antidiabetic drug, in mice infected with a very low dose of In contrast to diabetic mice, infected nondiabetic mice that received the same therapeutic concentration of MET presented with significantly higher disease burden. This warrants further studies to investigate the disparate efficacy of MET against tuberculosis in diabetic and nondiabetic individuals.

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Article Synopsis
  • * Type 2 diabetes (T2D) increases susceptibility to TB, but the exact mechanisms at play and the potential effectiveness of new vaccines in T2D patients remain unclear.
  • * Research using a diet-induced mouse model of T2D indicated that modified BCG vaccines enhance immune response and provide better protection against TB compared to conventional BCG, by improving immune cell function in diabetic mice.
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Tuberculosis (TB)-type 2 diabetes mellitus (T2D) comorbidity is re-emerging as a global public health problem. T2D is a major risk factor for increased susceptibility to TB infection and reactivation leading to higher morbidity and mortality. The pathophysiological mechanisms of T2D contributing to TB susceptibility are not fully understood, but likely involve dysregulated immune responses.

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The role of group A streptococcal and Streptococcus dysgalactiae subspecies equisimilis M-protein specific Abs and T-cells in endothelial cell activation was investigated using cultured rat aortic endothelial cells, and in a rat model of autoimmune valvulitis. Heat inactivated serum and mononuclear cells from streptococcal M-protein immunized rats independently induced upregulation of the endothelial cell adhesion molecules, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in cultured cells. We also observed T-cell migration across endothelial cell monolayers incubated with serum from M-protein-immunized rats.

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Background: Mycobacterium tuberculosis has co-evolved with the human host, adapting to exploit the immune system for persistence and transmission. While immunity to tuberculosis (TB) has been intensively studied in the lung and lymphoid system, little is known about the participation of adipose tissues and non-immune cells in the host-pathogen interaction during this systemic disease.

Methods: C57BL/6J mice were aerosol infected with M.

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Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are autoimmune mediated diseases triggered by group A streptococcal (GAS) infections. Molecular mimicry between GAS M-proteins and host tissue proteins has been proposed as the mechanism that initiates autoreactive immune responses in ARF/RHD. However, the individual role of antibodies and T-cells specific for GAS M-proteins in the pathogenesis of autoimmune carditis remains under-explored.

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Tuberculosis (TB) is a major global public health problem causing significant mortality and morbidity. In addition to ~10.4 million cases of active TB annually, it is estimated that about two billion people are latently infected with (), the causative agent of TB.

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