Publications by authors named "Malavige G"

Background: Elderly individuals, those with comorbidities and pregnant women are at a higher risk of developing severe dengue and succumbing to their illness. However, an increased incidence of severe dengue and fatalities are seen in females of the reproductive age. As per vaginal (PV) bleeding is an important complication that has not been well characterized, we sought to determine the frequency, complications and disease outcomes in women who develop PV bleeding.

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To face the current and emerging challenges due to infectious diseases, global research communities must comprehend the challenges faced by scientists in low-income and lower-middle-income countries. Here we address pertinent issues regarding funding and collaboration inequalities that could potentially cripple economic and healthcare systems, escalating to bigger global threats.

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Article Synopsis
  • Influenza A is a priority pathogen for the WHO due to its pandemic potential, leading to a study on its molecular epidemiology in the Western Province of Sri Lanka to inform vaccine selection and understand strain evolution.
  • The study involved 349 participants with respiratory symptoms, detecting Influenza A in 14%, B in 5.7%, and SARS-CoV-2 in 11.7% of cases, with some individuals having co-infections.
  • Genomic analysis revealed specific clades and subclades of H1N1 and H3N2 strains, along with several significant amino acid substitutions in the viral proteins, indicating ongoing viral evolution.
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Background: As many studies have shown conflicting results regarding the extent of viraemia and clinical disease severity, we sought to investigate if viraemia during early dengue illness is associated with subsequent clinical disease severity.

Methods: Realtime PCR was carried out to identify the dengue virus (DENV serotype), in 362 patients, presenting within the first 4 days of illness, from 2017 to 2022, in Colombo Sri Lanka. To characterize subsequent clinical disease severity, all patients were followed throughout their illness daily and disease severity classified according to WHO 1997 and 2009 disease classification.

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Article Synopsis
  • Influenza A is a significant concern for pandemics, prompting a study of its evolution in Sri Lanka to aid in vaccine selection.
  • A total of 349 patients with respiratory symptoms were analyzed, revealing that 14% had Influenza A, alongside lower rates of Influenza B and SARS-CoV-2, with several co-infections noted.
  • Findings included specific genetic clade classifications for H1N1 and H3N2 strains, along with multiple amino acid changes over time, highlighting the need for continuous monitoring of influenza viruses in the region.
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Background: We observed a discrepancy between dengue NS1 antigen test and molecular diagnostics, with the emergence of (DENV) serotype 3 in Sri Lanka and sought to understand the cause for the rise in cases and high failure rates of molecular diagnostics.

Methods: Whole genomic sequencing was carried out in 22 DENV-3 samples. Phylogenetic and molecular clock analysis were done for genotype assignment and to understand the rate of evolution.

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Asia remains vulnerable to new and emerging infectious diseases. Understanding how to improve next generation sequencing (NGS) use in pathogen surveillance is an urgent priority for regional health security. Here we developed a pathogen genomic surveillance assessment framework to assess capacity in low-resource settings in South and Southeast Asia.

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Article Synopsis
  • Researchers studied how the dengue virus affects patients early in their illness to see if the amount of virus (viraemia) is linked to how sick they get later.
  • They looked at 362 patients in Sri Lanka over several years and found that the type of dengue virus they had influenced the amount of virus in their bodies, but it didn't really change how severe their illness became.
  • In the end, they discovered that even though some dengue virus types led to lower viral loads, those infected with a specific type (DENV2) had a higher chance of getting very sick, but overall, the amount of virus didn’t predict how sick people would get.
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Background: The gut microbiome is thought to play an important role in the development of colorectal cancer (CRC). However, as the gut microbiome varies widely based on diet, we sought to investigate the gut microbiome changes in patients with CRC in a South Asian population.

Methods: The gut microbiome was assessed by 16s metagenomic sequencing targeting the V4 hypervariable region of the bacterial 16S rRNA in stool samples (n = 112) and colonic tissue (n = 36) in 112 individuals.

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Background: While dengue NS1 antigen has been shown to be associated with disease pathogenesis in some studies, it has not been linked in other studies, with the reasons remaining unclear. NS1 antigen levels in acute dengue are often associated with increased disease severity, but there has been a wide variation in results based on past dengue infection and infecting dengue virus (DENV) serotype. As NS1 engages with many host lipids, we hypothesize that the type of NS1-lipid interactions alters its pathogenicity.

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Article Synopsis
  • The study investigates the molecular epidemiology and evolutionary dynamics of influenza A in Sri Lanka's Western Province, emphasizing the need for genomic sequencing to inform seasonal vaccine selection amid pandemic concerns raised by the WHO.
  • From November 2022 to May 2024, researchers collected samples from 349 individuals with respiratory symptoms, finding influenza A in 14%, influenza B in 5.7%, and SARS-CoV-2 in 11.7% of participants, with some experiencing co-infections.
  • Phylogenetic analysis revealed specific clades and subclades for H1N1 and H3N2 strains, along with multiple amino acid substitutions in the H1N1 sequences between
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Purpose Of Review: With the marked rise in dengue globally, developing well tolerated and effective vaccines and therapeutics is becoming more important. Here we discuss the recent developments in the understanding of immune mechanisms that lead to severe dengue and the learnings from the past, that can help us to find therapeutic targets, prognostic markers, and vaccines to prevent development of severe disease.

Recent Findings: The extent and duration of viraemia often appears to be associated with clinical disease severity but with some variability.

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Background: Obesity and diabetes are known risk factors for severe dengue. Therefore, we sought to investigate the association of obesity with increased risk of hospitalization, as there is limited information.

Methods And Findings: Children aged 10 to 18 years (n = 4782), were recruited from 9 districts in Sri Lanka using a stratified multi-stage cluster sampling method.

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Historical legacies of colonialism affect the distribution and control of scientific knowledge today, including within the pathogen genomics field, which remains dominated by high-income countries (HICs). We discuss the imperatives for decolonising pathogen genomics, including the need for more equitable representation, collaboration, and capacity-strengthening, and the shared responsibilities that both low-income and middle-income countries (LMICs) and HICs have in this endeavour. By highlighting examples from LMICs, we illuminate the pathways and challenges that researchers in LMICs face in the bid to gain autonomy in this crucial domain.

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Background: While dengue NS1 antigen has been shown to be associated with disease pathogenesis in some studies, it has not been linked in other studies, with the reasons remaining unclear. NS1 antigen levels in acute dengue are often associated with increased disease severity, but there have been a wide variation in results based on past dengue infection and infecting dengue virus (DENV) serotype. As NS1 engages with many host lipids, we hypothesize that the type of NS1-lipid interactions alters its pathogenicity.

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As many other countries, Sri Lanka experienced a marked rise in the number of dengue cases in 2023, with an unusual pattern of disease epidemiology. This rise coincided with the emergence of dengue virus (DENV) serotype 3 in Sri Lanka as the predominant serotype after 2009. Interestingly, a discrepancy between NS1 rapid antigen test positivity and quantitative real time PCR positivity was observed, with 50% of NS1 positive samples being negative by molecular diagnostics.

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The SARS-CoV-2 genome occupies a unique place in infection biology - it is the most highly sequenced genome on earth (making up over 20% of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites.

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Background: Dengue poses a significant burden worldwide, and a more comprehensive understanding of the heterogeneity in the intensity of dengue transmission within endemic countries is necessary to evaluate the potential impact of public health interventions.

Methods: This scoping literature review aimed to update a previous study of dengue transmission intensity by collating global age-stratified dengue seroprevalence data published in the Medline, Embase and Web of Science databases from 2014 to 2023. These data were then utilised to calibrate catalytic models and estimate the force of infection (FOI), which is the yearly per-capita risk of infection for a typical susceptible individual.

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In 2023, Nepal faced its second largest dengue outbreak ever, following a record-breaking number of dengue cases in 2022, characterized by the expansion of infections into areas of higher altitudes. However, the characteristics of the 2023 circulating dengue virus (DENV) and the vector density remain poorly understood. Therefore, we performed DENV serotyping, clinical and laboratory assessment, and entomological analysis of the 2023 outbreak in central Nepal.

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Article Synopsis
  • * Many dengue patients are experiencing severe illness due to increased disease burden and shifting epidemiology, highlighting the need for better understanding of the disease.
  • * Researchers are exploring the molecular mechanisms of dengue pathogenesis and identifying significant knowledge gaps to facilitate the development of effective treatments, vaccines, and biomarkers.
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Dengue is the most rapidly emerging mosquito-borne infection and, due to climate change and unplanned urbanization, it is predicted that the global burden of dengue will rise further as the infection spreads to new geographical locations. Dengue-endemic countries are often unable to cope with such increases, with health care facilities becoming overwhelmed during each dengue season. Furthermore, although dengue has been predominantly a childhood illness in the past, it currently mostly affects adults in many countries, with higher incidence of severe disease and mortality rates in pregnant women and in those with comorbidities.

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