Identifying the strains of dengue circulating in the western province of Sri Lanka during 2019-2022.

A study conducted from July 2019 to May 2022 at several hospitals in the Western Province, Sri Lanka, focused on dengue virus strains during the COVID-19 pandemic. Among 417 febrile patients, 47% were PCR-positive for dengue. Serotyping revealed DENV-1 (12.

Identification of differentially recognized T cell epitopes in the spectrum of tuberculosis infection.

There is still incomplete knowledge of which Mycobacterium tuberculosis (Mtb) antigens can trigger distinct T cell responses at different stages of infection. Here, a proteome-wide screen of 20,610 Mtb-derived peptides in 21 patients mid-treatment for active tuberculosis (ATB) reveals IFNγ-specific T cell responses against 137 unique epitopes. Of these, 16% are recognized by two or more participants and predominantly derived from cell wall and cell processes antigens.

Host-response transcriptional biomarkers accurately discriminate bacterial and viral infections of global relevance.

Diagnostic limitations challenge management of clinically indistinguishable acute infectious illness globally. Gene expression classification models show great promise distinguishing causes of fever. We generated transcriptional data for a 294-participant (USA, Sri Lanka) discovery cohort with adjudicated viral or bacterial infections of diverse etiology or non-infectious disease mimics.

Serological Evidence of Circulation with Dengue and Chikungunya Infections in Sri Lanka from 2017.

Introduction: Arbovirus diseases remain a public health threat in Sri Lanka. Dengue is endemic and two outbreaks of chikungunya infections have been reported. There is limited data on Zika virus (ZIKV) infections in Sri Lanka, and this could be due to a lack of comprehensive ZIKV surveillance.

Identification of differentially recognized T cell epitopes in the spectrum of infection.

Tuberculosis caused by is one of the leading causes of death from a single infectious agent. Identifying dominant epitopes and comparing their reactivity in different tuberculosis (TB) infection states can help design diagnostics and vaccines. We performed a proteome-wide screen of 20,610 derived peptides in 21 Active TB (ATB) patients 3-4 months post-diagnosis of pulmonary TB (mid-treatment) using an IFNγ and IL-17 Fluorospot assay.

in soil and natural water bodies in rural Sri Lanka: A hidden threat to public health.

is the causative agent of the potentially fatal infection, melioidosis. This study provides the first evidence for the presence of in soil and water in Sri Lanka. Targeted sampling of soil and natural water sources was done between November 2019 and October 2020 over eight field visits encompassing the neighborhood of 28 culture and/or antibody-positive melioidosis patients in northwestern, western and southern Sri Lanka.

Single-cell profiling reveals distinct subsets of CD14+ monocytes drive blood immune signatures of active tuberculosis.

Introduction: Previous studies suggest that monocytes are an important contributor to tuberculosis (TB)-specific immune signatures in blood.

Methods: Here, we carried out comprehensive single-cell profiling of monocytes in paired blood samples of active TB (ATB) patients at diagnosis and mid-treatment, and healthy controls.

Results: At diagnosis, ATB patients displayed increased monocyte-to-lymphocyte ratio, increased frequency of CD14+CD16- and intermediate CD14+CD16+ monocytes, and upregulation of interferon signaling genes that significantly overlapped with previously reported blood TB signatures in both CD14+ subsets.

Correction: Outcomes among children and adults at risk of severe dengue in Sri Lanka: Opportunity for outpatient case management in countries with high disease burden.

[This corrects the article DOI: 10.1371/journal.pntd.

Transcriptomics of Acute DENV-Specific CD8+ T Cells Does Not Support Qualitative Differences as Drivers of Disease Severity.

While several lines of evidence suggest a protective role of T cells against disease associated with Dengue virus (DENV) infection, their potential contribution to immunopathology in the acute phase of DENV infection remains controversial, and it has been hypothesized that the more severe form of the disease (dengue hemorrhagic fever, DHF) is associated with altered T cell responses. To address this question, we determined the transcriptomic profiles of DENV-specific CD8+ T cells in a cohort of 40 hospitalized dengue patients with either a milder form of the disease (dengue fever, DF) or a more severe disease form (dengue hemorrhagic fever, DHF). We found multiple transcriptomic signatures, one associated with DENV-specific interferon-gamma responding cells and two other gene signatures, one specifically associated with the acute phase and the other with the early convalescent phase.

Current Understanding of the Role of T Cells in Chikungunya, Dengue and Zika Infections.

Arboviral infections such as Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) are a major disease burden in tropical and sub-tropical countries, and there are no effective vaccinations or therapeutic drugs available at this time. Understanding the role of the T cell response is very important when designing effective vaccines. Currently, comprehensive identification of T cell epitopes during a DENV infection shows that CD8 and CD4 T cells and their specific phenotypes play protective and pathogenic roles.

A Population of CD4CD8 Double-Positive T Cells Associated with Risk of Plasma Leakage in Dengue Viral Infection.

According to the WHO 2009 classification, dengue with warning signs is at the risk of developing severe form of dengue disease. One of the most important warning signs is plasma leakage, which can be a serious complication associated with higher morbidity and mortality. We report that the frequency of CD4CD8 double-positive (DP) T cells is significantly increased in patients at risk of developing plasma leakage.

Outcomes among children and adults at risk of severe dengue in Sri Lanka: Opportunity for outpatient case management in countries with high disease burden.

Background: Healthcare systems in dengue-endemic countries are often overburdened due to the high number of patients hospitalized according to dengue management guidelines. We systematically evaluated clinical outcomes in a large cohort of patients hospitalized with acute dengue to support triaging of patients to ambulatory versus inpatient management in the future.

Methods/principal Findings: From June 2017- December 2018, we conducted surveillance among children and adults with fever within the prior 7 days who were hospitalized at the largest tertiary-care (1,800 bed) hospital in the Southern Province, Sri Lanka.

Biogeography and genetic diversity of clinical isolates of Burkholderia pseudomallei in Sri Lanka.

Background: Melioidosis is a potentially fatal infectious disease caused by Burkholderia pseudomallei and the disease is endemic in Southeast Asia and Northern Australia. It has been confirmed as endemic in Sri Lanka. Genomic epidemiology of B.

Nonclonal Burkholderia pseudomallei Population in Melioidosis Case Cluster, Sri Lanka.

A melioidosis case cluster of 10 blood culture-positive patients occurred in eastern Sri Lanka after an extreme weather event. Four infections were caused by Burkholderia pseudomallei isolates of sequence type 594. Whole-genome analysis showed that the isolates were genetically diverse and the case cluster was nonclonal.

Evaluation of ELISA-Based Multiplex Peptides for the Detection of Human Serum Antibodies Induced by Zika Virus Infection across Various Countries.

Zika virus (ZIKV) is a mosquito-borne with a positive-sense RNA genome, which are generally transmitted through the bite of an infected mosquito. ZIKV infections could be associated with neurological sequelae that, and otherwise produces similar clinical symptoms as other co-circulating pathogens. Past infection with one member of the genus often induces cross-reactive antibodies against other flaviruses.

HLA-DR Marks Recently Divided Antigen-Specific Effector CD4 T Cells in Active Tuberculosis Patients.

Upon Ag encounter, T cells can rapidly divide and form an effector population, which plays an important role in fighting acute infections. In humans, little is known about the molecular markers that distinguish such effector cells from other T cell populations. To address this, we investigated the molecular profile of T cells present in individuals with active tuberculosis (ATB), where we expect Ag encounter and expansion of effector cells to occur at higher frequency in contrast to -sensitized healthy IGRA individuals.

Pre-existing T Cell Memory against Zika Virus.

The mosquito-borne Zika virus (ZIKV) has spread rapidly into regions where dengue virus (DENV) is endemic, and flavivirus cross-reactive T cell responses have been observed repeatedly in animal models and in humans. Preexisting cellular immunity to DENV is thought to contribute to protection in subsequent ZIKV infection, but the epitope targets of cross-reactive T cell responses have not been comprehensively identified. Using human blood samples from the regions of Nicaragua and Sri Lanka where DENV is endemic that were collected before the global spread of ZIKV in 2016, we employed an expansion strategy to map ZIKV T cell epitopes in ZIKV-unexposed, DENV-seropositive donors.

An increase in p62/NBR1 levels in melioidosis patients of Sri Lanka exhibit a characteristic of potential host biomarker.

Melioidosis, caused by , in endemic areas, poses a challenge for treating the diseased populations without accurate diagnosis, and the disease-specific biomarkers linked with the infection have yet to be reported. Due to the invasive nature of the causative agent, , host innate effector mechanisms, including autophagy are known to be activated, resulting in differential expression of cellular proteins and immune markers. Identification of a disease-specific biomarker associated with infection will be helpful to facilitate rapid confirmation of melioidosis, which would enable early treatment and therapeutic success.

T Cell Responses Induced by Attenuated Flavivirus Vaccination Are Specific and Show Limited Cross-Reactivity with Other Flavivirus Species.

Members of the flavivirus genus share a high level of sequence similarity and often circulate in the same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. In this study, we tested pools of epitopes derived from dengue (DENV), Zika (ZIKV), Japanese encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses by intracellular cytokine staining (ICS) using peripheral blood mononuclear cells (PBMCs) of individuals naturally exposed to DENV or immunized with DENV (TV005) or YF17D vaccine.

High Levels of Serum Angiopoietin 2 and Angiopoietin 2/1 Ratio at the Critical Stage of Dengue Hemorrhagic Fever in Patients and Association with Clinical and Biochemical Parameters.

Longitudinal changes of serum angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2) associated with endothelial stability in dengue patients with different disease stages were studied. Serum Ang-1 and Ang-2 levels were measured in confirmed dengue fever (DF) patients on admission (DFA,  = 40) and discharge (DFD,  = 20); in dengue hemorrhagic fever (DHF) patients on admission (DHFA,  = 40), at critical stage (DHFC,  = 36), and on discharge (DHFD,  = 20); and in healthy controls (HC,  = 25). DHFC had the highest serum Ang-2 and lowest Ang-1 levels compared to DFA, DHFA, and HC ( < 0.

Geospatial analysis of dengue emergence in rural areas in the Southern Province of Sri Lanka.

Background: Dengue is a major cause of acute febrile illness in Sri Lanka. Dengue has historically been considered an urban disease. In 2012-2013, we documented that acute dengue was surprisingly associated with self-reported rural residence in the Southern Province of Sri Lanka.

Molecular Signatures of Dengue Virus-Specific IL-10/IFN-γ Co-producing CD4 T Cells and Their Association with Dengue Disease.

Dengue virus (DENV) can cause diseases ranging from dengue fever (DF) to more severe dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Whether antiviral T cells contribute to the protection against or pathogenesis of severe disease is not well defined. Here, we identified antigen-specific IL-10IFN-γ double-positive (DP) CD4 T cells during acute DENV infection.