Gathsaurie Malavige

Gathsaurie Malavige
University of Sri Jayewardenepura · Immunology and Molecular Medicine

MBBS, MRCP, DPhil, FRCP, FRCPath

About

232
Publications
45,759
Reads
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3,661
Citations
Citations since 2016
162 Research Items
2546 Citations
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20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
Introduction
My main research area is to understand the immune mechanisms that lead to protection against severe dengue and also to understand the mechanisms that contribute to severe clinical disease.
Additional affiliations
September 2012 - present
University of Sri Jayewardenepura
Position
  • Director, Centre for Dengue Research
January 2011 - June 2015
University of Sri Jayewardenepura
Position
  • Head of Department
July 2008 - present
University of Oxford
Position
  • Academic visitor
Education
October 2004 - March 2008
University of Oxford
Field of study
  • Immunology
January 2003 - March 2005
Royal College of Physicians
Field of study
  • Medicine
January 1995 - April 2000
University of Colombo
Field of study
  • Medicine and Surgery

Publications

Publications (232)
Article
Full-text available
Although plasma leakage is the hallmark of severe dengue infections, the factors that cause increased vascular permeability have not been identified. As platelet activating factor (PAF) is associated with an increase in vascular permeability in other diseases, we set out to investigate its role in acute dengue infection. PAF levels were initially a...
Article
Full-text available
Currently there are no specific treatments available for acute dengue infection. We considered that rupatadine, a platelet-activating factor receptor inhibitor, might modulate dengue-associated vascular leak. The effects of rupatadine were assessed in vitro, and in a dengue model, which showed that rupatadine significantly reduced endothelial perme...
Article
Full-text available
The role of NS1-specific antibodies in the pathogenesis of dengue virus infection is poorly understood. Here we investigate the immunoglobulin responses of patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) to NS1. Antibody responses to recombinant-NS1 are assessed in serum samples throughout illness of patients with acute secondary...
Preprint
Full-text available
Severe pneumonia and multiorgan dysfunction in COVID-19 and dengue haemorrhagic fever (DHF) are two diseases that can associate with an altered immune response to the infecting virus. To determine the similarities and differences in the cytokine and chemokine responses in these two infections, we compared responses in patients with varying severity...
Article
Objective: We sought to investigate the differences in monocyte immune responses to the dengue virus (DENV) in those who previously had either severe disease (past SD) or non-severe dengue (past NSD) following a secondary dengue infection. Method: Monocytes from healthy individuals who had either past SD (n = 6) or past NSD (n = 6) were infected...
Article
Full-text available
Background Many countries in Asia and Latin America are currently facing a double burden of outbreaks due to dengue and COVID-19. Here we discuss the similarities and differences between the two infections so that lessons learnt so far from studying both infections will be helpful in further understanding their immunopathogenesis and to develop the...
Preprint
Full-text available
Background: To further understand the role of NS1 specific antibodies (Abs) in disease pathogenesis, we compared neutralizing antibody levels (Nabs), NS1-Ab levels, IgG antibody sub-class profiles and NS1 specific memory B cell responses (Bmems) in individuals, with varying severity of past dengue. Methods: Nabs (Neut50 titres) were assessed using...
Article
Full-text available
With the onset of the COVID-19 pandemic in early 2020 there was a drastic reduction in the number of dengue cases in Sri Lanka, with an increase towards the end of 2021. We sought to study the contribution of virological factors, human mobility, school closure and mosquito factors in affecting these changes in dengue transmission in Sri Lanka durin...
Article
Full-text available
Mast cell products and high levels of type 2 cytokines are associated with severe dengue disease. Group 2 innate lymphoid cells (ILC2) are type-2 cytokine-producing cells that are activated by epithelial cytokines and mast cell-derived lipid mediators. Through ex vivo RNAseq analysis, we observed that ILC2 are activated during acute dengue viral in...
Preprint
Background The dengue NS1 antigen is a secretory protein and was shown to associate with apolipoprotein A1 (ApoA1). Therefore, we sought to investigate the changes in ApoA1 levels in patients with varying severity of acute dengue and then proceeded to investigate how ApoA1 and NS1 interactions affect cytokine production from primary human monocytes...
Article
Full-text available
Background There are limited data regarding the safety and immunogenicity of the Sinopharm/BBIBP-CorV vaccine in pregnancy. Therefore, we sought to investigate the antibody responses and maternal and fetal adverse events following this vaccine in pregnant mothers in Sri Lanka. Methods and findings SARS-CoV-2 receptor binding domain (RBD) specific...
Article
Full-text available
We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bi...
Article
Full-text available
Background Rupatadine was previously shown to reduce endothelial dysfunction in vitro, reduced vascular leak in dengue mouse models and to reduce the extent of pleural effusions and thrombocytopenia in patients with acute dengue. Therefore, we sought to determine the efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever (DHF...
Article
Full-text available
Background The worst SARS-CoV-2 outbreak in Sri Lanka was due to the two Sri Lankan delta sub-lineages AY.28 and AY.104. We proceeded to further characterize the mutations and clinical disease severity of these two sub-lineages.Methods705 delta SARS-CoV-2 genomes sequenced by our laboratory from mid-May to November 2021 using Illumina and Oxford Na...
Article
Full-text available
Background: To determine the antibody responses elicited by different vaccines against SARS-CoV-2, we compared antibody responses in individuals 3 months post-vaccination in those who had received different vaccines in Sri Lanka. Methods: Abs to the RBD of the ancestral (wild type) virus (WT) as well as to variants of concern (VoCs), and ACE2 bl...
Article
Background: As there are limited data of the immunogenicity of the Sinopharm/BBIBP-CorV in different populations, antibody responses against different SARS-CoV-2 variants of concern and T cell responses, we investigated the immunogenicity of the vaccine, in individuals in Sri Lanka. Methods: SARS-CoV-2-specific antibodies were measured in 282 in...
Article
Full-text available
Background: To determine the kinetics and persistence of immune responses following the Sinopharm/BBIBP-CorV, we investigated immune responses in a cohort of Sri Lankan individuals. Methods: SARS-CoV-2 specific total antibodies were measured in 20-39 years (n = 61), 40-59 years (n = 120) and those >60 years of age (n = 22) by enzyme-linked immun...
Article
Background: Prevalence of antibody-mediated autoimmune encephalitis (AE) is reported to be comparable to infectious encephalitis in Western populations. We evaluated the frequency and significance of AE and neuronal autoantibodies in comparison to infectious etiologies among patients presenting with encephalitis in a South Asian population. Metho...
Article
Full-text available
As different SARS-CoV-2 variants emerge and with the continuous evolvement of sub lineages of the delta variant, it is crucial that all countries carry out sequencing of at least >1% of their infections, in order to detect emergence of variants with higher transmissibility and with ability to evade immunity. However, due to limited resources as man...
Article
Full-text available
Background: To understand the kinetics of immune responses with different dosing gaps of the AZD1222 vaccine, we compared antibody and T cell responses in two cohorts with two different dosing gaps. Methods: Antibodies to the SARS-CoV-2 virus were assessed in 297 individuals with a dosing gap of 12 weeks, sampled 12 weeks post second dose (cohor...
Article
Introduction and objectives: Dengue virus (DENV) NS1 is a non-structural secretory protein associated with severe disease and known to cause vascular leak leading to dengue haemorrhagic fever (DHF). As phospholipases A2 (PLA2) enzymes, platelet activating factor, and leukotrienes are elevated in dengue, we sought to investigate whether NS1 potentia...
Preprint
Full-text available
Background With the onset of the COVID-19 pandemic in early 2020 there was a drastic reduction in the number of dengue cases in Sri Lanka, with an increase towards the end of 2021. We sought to study the contribution of virological factors, human mobility, school closure and mosquito factors in affecting these changes in dengue transmission in Sri...
Article
Full-text available
Background SARS-CoV-2 rapid antigen (Ag) detection kits are widely used in addition to quantitative reverse transcription PCR PCR (RT-qPCR), as they are cheaper with a rapid turnaround time. As there are many concerns regarding their sensitivity and specificity, in different settings, we evaluated two WHO approved rapid Ag kits in a large cohort of...
Article
Full-text available
Purpose Surveillance of different SARS-CoV-2 variants of concern (VOCs) is a crucial aspect in control of the pandemic. Although sequencing is the gold-standard to detect VOCs, it is labor intensive and is costly. We compared a cost-effective real-time PCR assay that detects single nucleotide polymorphisms (SNPs) of VOCs, with next generation seque...
Article
Full-text available
Purpose The dosing interval for AZD1222/Covishield vaccine was prolonged for ≥16 weeks, due to short supply in Sri Lanka. As robust secondary immune response depends on the presence of memory B cell (Bmem), we investigated their frequency following a single dose of the AZD1222. Methods & Materials Bmem responses were assessed to S1, S2 and N prote...
Article
Full-text available
Purpose Despite the rollout of several vaccines targeting SARS-CoV-2, attainment of near-universal vaccination is a challenging task, particularly for low- and middle-income nations such as Sri Lanka. Rapid, reliable diagnostics for the detection of the virus is of vital importance for the predominantly export- and tourism-based economy of the coun...
Article
Full-text available
Purpose Jaffna, which is in the Northern Province of Sri Lanka has been experiencing an increase in the number of dengue infections in recent years. Therefore, it would be important to identify the emergence of different dengue virus (DENV) serotypes in the province to understand the changing epidemiology of dengue and to initiate timely control me...
Article
Full-text available
Purpose As experienced by many countries, Sri Lanka is currently experiencing a large COVID-19 outbreak, with over 90 cases/one million population. The previous outbreak, which was due to the B.1.411 virus (Sri Lankan lineage) resulted in a significantly fewer number of cases and deaths compared to the current outbreak caused by B.1.1.7. Therefore,...
Preprint
Full-text available
Background The worst SARS-CoV-2 outbreak in Sri Lanka was due to the two Sri Lankan delta sub-lineages AY.28 and AY.104. We proceeded to further characterize the mutations and clinical disease severity of these two sub-lineages. Methods 705 delta SARS-CoV-2 genomes sequenced by our laboratory from mid-May to November 2021 using Illumina and Oxford...
Article
Full-text available
As the first dose of Gam-COVID-Vac, is currently used as a single dose vaccine in some countries, we investigated the immunogenicity of this at 4 weeks (327 naïve individuals). 88.7% seroconverted, with significantly lower seroconversion rates in those over 60 years (p = 0.004) and significantly lower than previously seen with AZD1222 (p = 0.018)....
Article
Full-text available
To characterize the IgG and IgA responses to different SARS-CoV-2 proteins, we investigated the antibody responses to SARS-CoV-2 following natural infection and following a single dose of AZD1222(Covishield), in Sri Lankan individuals. The IgG and IgA responses were assessed to S1, S2, RBD and N proteins in patients at 4 weeks and 12 weeks since on...
Article
Although the scientific community had been predicting and preparing for a pandemic for the last 10 years, many policy makers did not envision that a virus could cause such devastation to human life, economies and to the social structure. COVID-19 has taught us many bitter lessons and while moving forward it is important to understand that this curr...
Preprint
Full-text available
We assessed antibody responses 3 months post-vaccination in those who received mRNA-1273 (n=225), Sputnik V (n=128) or the first dose of Gam-COVID-Vac (n=184) and compared the results with previously reported data of Sinopharm and AZD1222 vaccinees. 99.5% of Moderna >94% of AZD1222 or Sputnik V, 72% to 76% of Gam-COVID-Vac (first dose) and 38.1% to...
Preprint
Full-text available
As different SARS-CoV-2 variants emerge and with the continuous evolution of sub-lineages of the delta and other variants, it is crucial that all countries carry out sequencing of at least >1% of their infections, in order to detect emergence of variants with higher transmissibility and with ability to evade immunity. However, as many resource-poor...
Article
Background Although active surveillance SARS-CoV-2 variants of concern (VOCs) is required for proper outbreak control measures, many lower income countries find it challenging to detect VOCs) by carrying genomic sequencing alone, due to limited resources. Methods VOCs can also be identified by the unique mutations in the spike protein by real-time...
Article
Full-text available
Background: As the Municipality Council area in Colombo (CMC) experienced the highest number of cases until the end of January 2021, in Sri Lanka, we carried out a serosurvey prior to initiation of the vaccination program to understand the extent of the SARS-CoV-2 outbreak. Methods: SARS-CoV-2 seropositivity was determined in 2,547 individuals betw...
Article
Full-text available
Dengue is a significant health concern in Sri Lanka, but diagnosis of the infecting dengue virus (DENV) serotype has hitherto been largely restricted to the Colombo district in the western province. Salinity tolerant Aedes vectors are present in the island's northern Jaffna peninsula, which is undergoing rapid groundwater salinization. Virus seroty...
Article
Full-text available
Due to limited access to vaccines, many countries have only administered a single dose of the AZD1222, whereas the dosage intervals have increased ≥4 wk. We sought to investigate the immunogenicity of a single dose of vaccine at ≥16 wk postimmunization. Severe acute respiratory syndrome coronavirus 2-specific Abs in 553 individuals and Abs to the r...
Article
Full-text available
Background The transmission dynamics of SARS-CoV-2 varies depending on social distancing measures, circulating SARS-CoV-2 variants, host factors and other environmental factors. We sought to investigate the clinical and epidemiological characteristics of a SARS-CoV-2 outbreak that occurred in a highly dense population area in Colombo, Sri Lanka fro...
Article
Full-text available
Background The natural antibody responses to B-cell epitopes from dengue structural proteins were assessed using immune sera from people having well-defined past dengue infections with one of the four serotypes. Method Based on an immune-computational analysis previously conducted, nineteen epitopes from the envelope (E) and eight epitopes from pr...
Article
Dengue is among the deadliest insect-borne diseases circulating in Sri Lanka. Most of the infections that are diagnosed early are manageable. However, delays in diagnosis may cause fatalities. We evaluated the dengue NS1 antigen card and NS1 SD kit for early diagnosis of dengue using samples from 116 RT-PCR-positive patients admitted within 5 days...
Preprint
Full-text available
Background To understand the kinetics of immune responses with different dosing gaps of the AZD1222 vaccine, we compared antibody and T cell responses in two cohorts with two different dosing gaps. Methods Antibodies to the SARS-CoV-2 virus were assessed in 297 individuals with a dosing gap of 12 weeks, sampled at 12 weeks post second dose (cohort...
Preprint
Full-text available
Background: To determine the kinetics and persistence of immune responses following the Sinopharm/BBIBP-CorV, we investigated immune responses in a cohort of Sri Lankan individuals. Methods: SARS-CoV-2 specific total antibodies were measured in 20-to-39 year (n=61), 40-to-59-year and those >60 years of age (n=22) by ELISA, 12 weeks after the second...
Conference Paper
Full-text available
Introduction: Asthma is a major childhood illness. Studies have shown associations between aeroallergen exposure and asthma globally Objectives: To evaluate the association between aeroallergen sensitivity and asthma control in children with asthma attending a specialist child care hospital and to compare these findings with a study from the same c...
Article
Full-text available
Background: In order to understand the molecular epidemiology of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Sri Lanka, since March 2020, we carried out genomic sequencing overlaid on available epidemiological data until April 2021. Methods: Whole genome sequencing was carried out on diagnostic sputum or nasopharyngeal swabs fro...
Article
Full-text available
Background Dengue infections are on the rise in Sri Lanka and are spreading to all areas in the country. Here, we discuss the changes in dengue epidemiology in Sri Lanka in relation to changes in age distribution, changes in seroprevalence rates over time, and possible reasons contributing to such changes. Methods and findings Although the inciden...
Preprint
Full-text available
As the first dose of Gam-COVID-Vac, is currently used as a single dose vaccine in some countries, we investigated the immunogenicity of this at 4 weeks (327 naïve individuals). 88.7% seroconverted, with significantly lower seroconversion rates in those over 60 years (p = 0.004) and significantly lower than previously seen with AZD1222 (p = 0.018)....
Preprint
Full-text available
As the first dose of Gam-COVID-Vac, is currently used as a single dose vaccine in some countries, we investigated the immunogenicity of this at 4 weeks (327 naïve individuals). 88.7% seroconverted, with significantly lower seroconversion rates in those over 60 years (p = 0.004) and significantly lower than previously seen with AZD1222 (p = 0.018)....
Article
Full-text available
Several COVID-19 vaccines have received emergency approval. Here we assess the immu-nogenicity of a single dose of the AZD1222 vaccine, at one month, in a cohort of health care workers (HCWs) (629 naïve and 26 previously infected). 93.4% of naïve HCWs ser-oconverted, irrespective of age and gender. Haemagglutination test for antibodies to the recep...
Preprint
Full-text available
Introduction: Due to limited access to vaccines, many countries have only administered a single dose of the AZD1222, while the dosage intervals have increased ≥ weeks. We sought to investigate the immunogenicity of a single dose of vaccine at ≥ 16 weeks. Methods: SARS-CoV-2 specific antibodies in 553 individuals and antibodies to the receptor bindi...
Preprint
Full-text available
As there are limited data of the immunogenicity of the Sinopharm/BBIBP-CorV in different populations, antibody responses against different SARS-CoV-2 variants of concern and T cell responses, we investigated the immunogenicity of the vaccine, in individuals in Sri Lanka.
Preprint
Full-text available
Background: While there have been many studies characterizing the IgG and IgA responses to different SARS-CoV-2 proteins in individuals with natural infection, the induction of IgG and IgA to different viral proteins in vaccinees have not been extensively studied. Therefore, we sought to investigate the antibody responses to SARS-CoV-2 following na...
Preprint
Full-text available
Background As the Municipality Council area in Colombo (CMC) experienced the highest number of cases until end of January 2021, in Sri Lanka, we carried out a serosurvey prior to initiation of the vaccination program to understand the extent of the SARS-CoV-2 outbreak. Methods SARS-CoV-2 seropositivity was determined in 2547 individuals between the...
Preprint
Full-text available
Background: SARS-CoV-2 rapid antigen (Ag) detection kits are widely used in addition to quantitative real-time PCR (RT-qPCR), as they are cheaper with a rapid turnaround