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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. Although the incidence of dengue increased 20-fold from the year 2000 to 2012 and a further 3-fold from 2012 to 2019, this increase is not reflected in a similar increase in the age-stratified seropositivity rates for dengue. For instance, the annual seroconversion rates were 0.76% in 2013 and 0.91% in 2017. The annual seroconversion rates in the 6 to 17 age group were 1.5% per year in 2003, 3.9% in 2013, and 4.1% in 2017. In addition, although a 13-fold increase in dengue was seen in those who were <19 years of age, a 52.4-fold increase was seen in the 40- to 59-year age group. The case fatality rates (CFRs) have similarly changed, with 61.8% of deaths occurring in those <19 years of age in the year 2000, while in 2012 to 2018, the highest CFR were seen in those who were aged 20 to 39 years. Although there has been a marked increase in the number of cases, the vector densities did not change during a 4-year period. The proportion of adult individuals experiencing a secondary dengue infection has also remained between 65% and 75% between the years 2004 and 2018. A change in the ratio of symptomatic to asymptomatic infections can give rise to changes in the reported incidence of dengue. In order to take an appropriate policy decision in dengue control activities, it would be important to study the changes in virus serotypes, vector dispersion, and densities. Further, the contribution of the rise in metabolic diseases to an increase in the symptomatic as well as more severe infections due to dengue is explored.
Gathsaurie Neelika Malavige; Chandima Jeewandara; Azhar Ghouse; Gayasha Somathilake; Hasitha Tissera. Changing epidemiology of dengue in Sri Lanka—Challenges for the future. 2021, 15, 1 .
AMA StyleGathsaurie Neelika Malavige, Chandima Jeewandara, Azhar Ghouse, Gayasha Somathilake, Hasitha Tissera. Changing epidemiology of dengue in Sri Lanka—Challenges for the future. . 2021; 15 (8):1.
Chicago/Turabian StyleGathsaurie Neelika Malavige; Chandima Jeewandara; Azhar Ghouse; Gayasha Somathilake; Hasitha Tissera. 2021. "Changing epidemiology of dengue in Sri Lanka—Challenges for the future." 15, no. 8: 1.
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). 82.6% developed ACE2 receptor blocking antibodies, although levels were significantly lower than following natural infection (p = 0.0009) and a single dose of AZD1222 (p < 0.0001). Similar titres of antibodies were observed to the receptor binding domain of WT, B.1.1.7 and B.1.617.2 compared to AZD1222, while the levels for B.1.351 were significantly higher (p = 0.006) for Gam-COVID-Vac. 30% developed ex vivo IFNγ ELISpot responses (significantly lower than AZD1222), and high frequency of CD107a expressing T cells along with memory B cell responses. Although single dose of Gam-COVID-Vac was highly immunogenic, administration of a second dose is likely to be beneficial.
Chandima Jeewandara; Harsha Fernando; Pradeep Pushpakumara; Shyrar Tanussiya; Achala Kamaladasa; Banuri Gunasekara; Inoka Aberathna; Heshan Kuruppu; Thushali Ranasinghe; Shashika Dayarathne; Osanda Dissanayaka; Nayanathara Gamalath; Dinithi Ekanayaka; Mpdj Jayamali; Ayesha Wijesinghe; Madushika Dissanayake; Gayasha Somathilaka; Michael Harvie; Saubhagya Danasekara; Deshni Jayathilaka; Dinesh Wijayathilaka; Nihal Weerasooriya; Chinthaka Kekulandara; Lisa Schimanski; Pramila Rijal; Tiong Kit Tan; Tao Dong; Alain Townsend; Graham Ogg; Gathsaurie Malavige. Immune responses following the first dose of the Sputnik V (Gam-COVID-Vac). 2021, 1 .
AMA StyleChandima Jeewandara, Harsha Fernando, Pradeep Pushpakumara, Shyrar Tanussiya, Achala Kamaladasa, Banuri Gunasekara, Inoka Aberathna, Heshan Kuruppu, Thushali Ranasinghe, Shashika Dayarathne, Osanda Dissanayaka, Nayanathara Gamalath, Dinithi Ekanayaka, Mpdj Jayamali, Ayesha Wijesinghe, Madushika Dissanayake, Gayasha Somathilaka, Michael Harvie, Saubhagya Danasekara, Deshni Jayathilaka, Dinesh Wijayathilaka, Nihal Weerasooriya, Chinthaka Kekulandara, Lisa Schimanski, Pramila Rijal, Tiong Kit Tan, Tao Dong, Alain Townsend, Graham Ogg, Gathsaurie Malavige. Immune responses following the first dose of the Sputnik V (Gam-COVID-Vac). . 2021; ():1.
Chicago/Turabian StyleChandima Jeewandara; Harsha Fernando; Pradeep Pushpakumara; Shyrar Tanussiya; Achala Kamaladasa; Banuri Gunasekara; Inoka Aberathna; Heshan Kuruppu; Thushali Ranasinghe; Shashika Dayarathne; Osanda Dissanayaka; Nayanathara Gamalath; Dinithi Ekanayaka; Mpdj Jayamali; Ayesha Wijesinghe; Madushika Dissanayake; Gayasha Somathilaka; Michael Harvie; Saubhagya Danasekara; Deshni Jayathilaka; Dinesh Wijayathilaka; Nihal Weerasooriya; Chinthaka Kekulandara; Lisa Schimanski; Pramila Rijal; Tiong Kit Tan; Tao Dong; Alain Townsend; Graham Ogg; Gathsaurie Malavige. 2021. "Immune responses following the first dose of the Sputnik V (Gam-COVID-Vac)." , no. : 1.
Several COVID-19 vaccines have received emergency approval. Here we assess the immunogenicity 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 seroconverted, irrespective of age and gender. Haemagglutination test for antibodies to the receptor binding domain (RBD), surrogate neutralization assay (sVNT) and ex vivo IFNγ ELISpot assays were carried out in a sub-cohort. ACE2 blocking antibodies (measured by sVNT) were detected in 67/69 (97.1%) of naïve HCWs. Antibody levels to the RBD of the wild-type virus were higher than to RBD of B.1.1.7, and titres to B.1.351 were very low. Ex vivo T cell responses were observed in 30.8% to 61.7% in naïve HCWs. Previously infected HCWs, developed significantly higher (p < 0.0001) ACE2 blocking antibodies and antibodies to the RBD for the variants B.1.1.7 and B.1.351. This study shows high seroconversion after one vaccine dose, but also suggests that one vaccine dose may be insufficient to protect against emerging variants.
Chandima Jeewandara; Achala Kamaladasa; Pradeep Darshana Pushpakumara; Deshni Jayathilaka; Inoka Sepali Aberathna; Danasekara Rallage Saubhagya Rasikangani Danasekara; Dinuka Guruge; Thushali Ranasinghe; Shashika Dayarathna; Thilagaraj Pathmanathan; Gayasha Somathilake; Panambara Arachchige Deshan Madhusanka; Shyrar Tanussiya Ramu; Tibutius Thanesh Pramanayagam Jayadas; Heshan Kuruppu; Ayesha Wijesinghe; Herath Mudiyanselage Thashmi Nimasha; Dushantha Milroy; Achini Anuja Nandasena; Poththawela Kankanam Gamage Nilanka Sanjeewani; Ruwan Wijayamuni; Sudath Samaraweera; Lisa Schimanski; T. K. Tan; Tao Dong; Graham S. Ogg; Alain Townsend; Gathsaurie Neelika Malavige. Immune responses to a single dose of the AZD1222/Covishield vaccine in health care workers. Nature Communications 2021, 12, 1 -9.
AMA StyleChandima Jeewandara, Achala Kamaladasa, Pradeep Darshana Pushpakumara, Deshni Jayathilaka, Inoka Sepali Aberathna, Danasekara Rallage Saubhagya Rasikangani Danasekara, Dinuka Guruge, Thushali Ranasinghe, Shashika Dayarathna, Thilagaraj Pathmanathan, Gayasha Somathilake, Panambara Arachchige Deshan Madhusanka, Shyrar Tanussiya Ramu, Tibutius Thanesh Pramanayagam Jayadas, Heshan Kuruppu, Ayesha Wijesinghe, Herath Mudiyanselage Thashmi Nimasha, Dushantha Milroy, Achini Anuja Nandasena, Poththawela Kankanam Gamage Nilanka Sanjeewani, Ruwan Wijayamuni, Sudath Samaraweera, Lisa Schimanski, T. K. Tan, Tao Dong, Graham S. Ogg, Alain Townsend, Gathsaurie Neelika Malavige. Immune responses to a single dose of the AZD1222/Covishield vaccine in health care workers. Nature Communications. 2021; 12 (1):1-9.
Chicago/Turabian StyleChandima Jeewandara; Achala Kamaladasa; Pradeep Darshana Pushpakumara; Deshni Jayathilaka; Inoka Sepali Aberathna; Danasekara Rallage Saubhagya Rasikangani Danasekara; Dinuka Guruge; Thushali Ranasinghe; Shashika Dayarathna; Thilagaraj Pathmanathan; Gayasha Somathilake; Panambara Arachchige Deshan Madhusanka; Shyrar Tanussiya Ramu; Tibutius Thanesh Pramanayagam Jayadas; Heshan Kuruppu; Ayesha Wijesinghe; Herath Mudiyanselage Thashmi Nimasha; Dushantha Milroy; Achini Anuja Nandasena; Poththawela Kankanam Gamage Nilanka Sanjeewani; Ruwan Wijayamuni; Sudath Samaraweera; Lisa Schimanski; T. K. Tan; Tao Dong; Graham S. Ogg; Alain Townsend; Gathsaurie Neelika Malavige. 2021. "Immune responses to a single dose of the AZD1222/Covishield vaccine in health care workers." Nature Communications 12, no. 1: 1-9.
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 binding domain (RBD) of the Wuhan virus (WT) and the variants of concern (VOCs), ACE2 receptor blocking antibodies, ex vivo and cultured IFNγ T cell responses and B cell ELISpot responses were investigated in a sub-cohort. Results The seropositivity rates in those >70 years of age (93.7%) was not significantly different compared to other age groups (97.7 to 98.2, Pearson Chi-Square = 7.8, p-value = 0.05). The antibody titres (antibody index) significantly declined (p60 years. Ex vivo IFN γ T cell ELISpot responses were seen in 10/66 (15.1%), while only a few expressed CD107a. However, >85% had a high frequency of cultured IFNγ T cell ELISpot responses and B cell ELISpots. Conclusion Virus specific antibodies were maintained at ≥ 16 weeks after receiving a single dose of AZD1222, although levels were lower to VOCs, especially in older individuals. A single dose induced a high frequency of memory T and B cell responses.
Chandima Jeewandara; Dinuka Guruge; Pradeep Darshana Pushpakumara; Achala Kamaladasa; Inoka Sepali Aberathna; Shyrar Tanussiya; B Banuri Gunasekera; Ayesha Wijesinghe; Osanda Dissanayake; Heshan Kuruppu; Thushali Ranasinghe; Deshni Jayathilaka; Shashika Dayarathna; Dinithi Ekanayake; Mpdj Jayamali; Nayanathara Gamalath; Anushika Mudumkotuwa; Gayasha Somathilake; Madhushika Dissanayake; Michael Harvie; Thashmi Nimasha; Deshan Madusanka; Tibutius Jayadas; Ruwan Wijayamuni; Lisa Schimanski; Pramila Rijal; Tiong .K. Tan; Alain Townsend; Graham S. Ogg; Gathsaurie Neelika Malavige. Immune responses to a single dose of the AZD1222/Covishield vaccine at 16 weeks in individuals in Sri Lanka. 2021, 1 .
AMA StyleChandima Jeewandara, Dinuka Guruge, Pradeep Darshana Pushpakumara, Achala Kamaladasa, Inoka Sepali Aberathna, Shyrar Tanussiya, B Banuri Gunasekera, Ayesha Wijesinghe, Osanda Dissanayake, Heshan Kuruppu, Thushali Ranasinghe, Deshni Jayathilaka, Shashika Dayarathna, Dinithi Ekanayake, Mpdj Jayamali, Nayanathara Gamalath, Anushika Mudumkotuwa, Gayasha Somathilake, Madhushika Dissanayake, Michael Harvie, Thashmi Nimasha, Deshan Madusanka, Tibutius Jayadas, Ruwan Wijayamuni, Lisa Schimanski, Pramila Rijal, Tiong .K. Tan, Alain Townsend, Graham S. Ogg, Gathsaurie Neelika Malavige. Immune responses to a single dose of the AZD1222/Covishield vaccine at 16 weeks in individuals in Sri Lanka. . 2021; ():1.
Chicago/Turabian StyleChandima Jeewandara; Dinuka Guruge; Pradeep Darshana Pushpakumara; Achala Kamaladasa; Inoka Sepali Aberathna; Shyrar Tanussiya; B Banuri Gunasekera; Ayesha Wijesinghe; Osanda Dissanayake; Heshan Kuruppu; Thushali Ranasinghe; Deshni Jayathilaka; Shashika Dayarathna; Dinithi Ekanayake; Mpdj Jayamali; Nayanathara Gamalath; Anushika Mudumkotuwa; Gayasha Somathilake; Madhushika Dissanayake; Michael Harvie; Thashmi Nimasha; Deshan Madusanka; Tibutius Jayadas; Ruwan Wijayamuni; Lisa Schimanski; Pramila Rijal; Tiong .K. Tan; Alain Townsend; Graham S. Ogg; Gathsaurie Neelika Malavige. 2021. "Immune responses to a single dose of the AZD1222/Covishield vaccine at 16 weeks in individuals in Sri Lanka." , no. : 1.
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 natural infection and following a single dose of AZD2221, in Sri Lankan individuals. Methods: Using Luminex assays, we characterized the IgG and IgA responses in patients with varying severity of illness and following a single dose of the vaccine at 4 weeks and 12 weeks since onset of illness or following vaccination. Haemagglutination test (HAT) was used to assess the antibodies to the receptor binding domain of SARS-CoV-2 wild type (WT), B.1.1.7, B.1.351 and B.1.617.2 (VOCs) and surrogate neutralizing test to measure ACE2 receptor blocking antibodies. Results: Those with mild illness and in vaccinees, the IgG responses to S1, S2, RBD and N protein increased from 4 weeks to 12 weeks, while it remained unchanged in those with moderate/severe illness. Those who had a febrile illness in 2017 and 2018 (controls) also gave IgG and IgA high responses to the S2 subunit. In the vaccinees, the most significant rise was seen for the IgG antibodies to the S2 subunit (p<0.0001). Vaccinees had several fold lower IgA antibodies to all the SARS-CoV-2 proteins tested than those with mild and moderate/severe illness at 4 weeks and 12 weeks. At 12 weeks the HAT titres were significantly lower to the B.1.1.7 in vaccinees and significantly lower in those with mild illness, and in vaccinees to B.1.351 and for B.1.617.2. No such difference was seen in those with moderate/severe illness. Conclusions: Vaccinees had significantly less IgA to SARS-CoV-2, but comparable IgG responses to those with natural infection. However, following a single dose, vaccinees had reduced antibody levels to the variants of concern (VOC), which further declined with time, compared to natural infection.
Deshni Jayathilaka; Chandima Jeewandara; Laksiri Gomes; Tibutius Thanesh Pramanayagam Jayadas; Achala Kamaladasa; Dinuka Guruge; Pradeep Pushpakumara; Thushali Ranasinghe; Inoka Abayratne; Saubhagya Danasekara; Buddhini Gunathilaka; Heshan Kuruppu; Ananda Wijewickrama; Ruwan Wijayamuni; Lisa Schimanski; Tiong Tan; Graham S. Ogg; Alain Townsend; Gathsaurie Neelika Malavige. Comparison of kinetics of immune responses to SARS-CoV-2 proteins in individuals with varying severity of infection and following a single dose of the AZD1222. 2021, 1 .
AMA StyleDeshni Jayathilaka, Chandima Jeewandara, Laksiri Gomes, Tibutius Thanesh Pramanayagam Jayadas, Achala Kamaladasa, Dinuka Guruge, Pradeep Pushpakumara, Thushali Ranasinghe, Inoka Abayratne, Saubhagya Danasekara, Buddhini Gunathilaka, Heshan Kuruppu, Ananda Wijewickrama, Ruwan Wijayamuni, Lisa Schimanski, Tiong Tan, Graham S. Ogg, Alain Townsend, Gathsaurie Neelika Malavige. Comparison of kinetics of immune responses to SARS-CoV-2 proteins in individuals with varying severity of infection and following a single dose of the AZD1222. . 2021; ():1.
Chicago/Turabian StyleDeshni Jayathilaka; Chandima Jeewandara; Laksiri Gomes; Tibutius Thanesh Pramanayagam Jayadas; Achala Kamaladasa; Dinuka Guruge; Pradeep Pushpakumara; Thushali Ranasinghe; Inoka Abayratne; Saubhagya Danasekara; Buddhini Gunathilaka; Heshan Kuruppu; Ananda Wijewickrama; Ruwan Wijayamuni; Lisa Schimanski; Tiong Tan; Graham S. Ogg; Alain Townsend; Gathsaurie Neelika Malavige. 2021. "Comparison of kinetics of immune responses to SARS-CoV-2 proteins in individuals with varying severity of infection and following a single dose of the AZD1222." , no. : 1.
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 ages of 10 to 86 years, by the Wantai total antibody ELISA. We also compared to seroprevalence using the haemagglutination test (HAT) to evaluate its usefulness in carrying out serosurveys. Results The overall seropositivity rate was 24.46%, while seropositivity by HAT was 18.9%. Although the SARS-CoV-2 infection detection rates by PCR were highest in the population between the ages of 20 to 60 years of age, the seropositivity rates were equal among all age groups. The seropositivity rate was highest in the 10 to 20 age group (34.03%), whereas the PCR positivity rates was 9.8%. Differences in the PCR positivity rates and seropositivity rates were also seen in 60- to 70-year-olds (8.9% vs 30.4%) and in individuals >70 year (4.1% vs 1.2%). The seropositivity rates of the females was 29.7% (290/976), which was significantly higher (p<0.002) than in males 21.2% (333/1571). Conclusions A high seroprevalence rate (24.5%) was seen in all age groups in the CMC suggesting that a high level of transmission was seen during this area. The PCR positivity rates, appear to underestimate the true extent of the outbreak and the age groups which were infected.
Chandima Jeewandara; Dinuka Guruge; Inoka S Aberathna; Saubhagya Danasekara; Banuri Gunasekara; Pradeep Darshana Pushpakumara; Deshan Madushanka; Deshni Jayathilaka; Thushali Ranasinghe; Gayasha Somathilaka; Shyrar Tanussiya; Tibutius Tanesh Jayadas; Heshan Kuruppu; Nimasha Thashmi; Michael Harvie; Ruwan Wijayamuni; Lisa Schimanski; Tiong Tan; Pramila Rijal; Julie Xiao; Graham S. Ogg; Alain Townsend; Gathsaurie Neelika Malavige. Seroprevalence of SARS-CoV-2 infection in the Colombo Municipality region, Sri Lanka. 2021, 1 .
AMA StyleChandima Jeewandara, Dinuka Guruge, Inoka S Aberathna, Saubhagya Danasekara, Banuri Gunasekara, Pradeep Darshana Pushpakumara, Deshan Madushanka, Deshni Jayathilaka, Thushali Ranasinghe, Gayasha Somathilaka, Shyrar Tanussiya, Tibutius Tanesh Jayadas, Heshan Kuruppu, Nimasha Thashmi, Michael Harvie, Ruwan Wijayamuni, Lisa Schimanski, Tiong Tan, Pramila Rijal, Julie Xiao, Graham S. Ogg, Alain Townsend, Gathsaurie Neelika Malavige. Seroprevalence of SARS-CoV-2 infection in the Colombo Municipality region, Sri Lanka. . 2021; ():1.
Chicago/Turabian StyleChandima Jeewandara; Dinuka Guruge; Inoka S Aberathna; Saubhagya Danasekara; Banuri Gunasekara; Pradeep Darshana Pushpakumara; Deshan Madushanka; Deshni Jayathilaka; Thushali Ranasinghe; Gayasha Somathilaka; Shyrar Tanussiya; Tibutius Tanesh Jayadas; Heshan Kuruppu; Nimasha Thashmi; Michael Harvie; Ruwan Wijayamuni; Lisa Schimanski; Tiong Tan; Pramila Rijal; Julie Xiao; Graham S. Ogg; Alain Townsend; Gathsaurie Neelika Malavige. 2021. "Seroprevalence of SARS-CoV-2 infection in the Colombo Municipality region, Sri Lanka." , no. : 1.
Background Neutralizing antibodies (NAbs) are important for protection against COVID-19 re-infection. We compared two assays that are correlated with NAbs, the haemagglutination test (HAT) and surrogate virus neutralization test (sVNT). Methods The specificity of the HAT was compared with the sVNT and the sensitivity and persistence of antibodies in patients with varying severity of illness was assessed in cohort of 71 patients at 4 to 6 weeks and 13-16 weeks. The kinetics was assessed in first, second and third week in patients with varying severity of acute illness. Results The specificity of the HAT was >99%, and sensitivity was similar to lower than the sVNT. The levels of HAT significantly and positively correlated (Spearman's r=0.78, p1:640 during the second week of illness, whereas only 5/31 patients with mild illness had a titre of >1:160 in the second week of illness. Conclusions Since the HAT is a simple, and very cheap assay to perform, it would be ideal to use as an indicator of NAbs in resource-poor settings.
Achala Kamaladasa; Banuri Gunasekara; Chandima Jeewandara; Deshni Jayathilaka; Ananda Wijewickrama; Dinuka Guruge; Ruwan Wijayamuni; T.K. Tan; Graham S. Ogg; Alain Townsend; Gathsaurie Neelika Malavige. Comparison of two assays to detect IgG antibodies to the receptor binding domain of SARS‑CoV‑2 as a surrogate marker for assessing neutralizing antibodies in COVID-19 patients. International Journal of Infectious Diseases 2021, 109, 85 -89.
AMA StyleAchala Kamaladasa, Banuri Gunasekara, Chandima Jeewandara, Deshni Jayathilaka, Ananda Wijewickrama, Dinuka Guruge, Ruwan Wijayamuni, T.K. Tan, Graham S. Ogg, Alain Townsend, Gathsaurie Neelika Malavige. Comparison of two assays to detect IgG antibodies to the receptor binding domain of SARS‑CoV‑2 as a surrogate marker for assessing neutralizing antibodies in COVID-19 patients. International Journal of Infectious Diseases. 2021; 109 ():85-89.
Chicago/Turabian StyleAchala Kamaladasa; Banuri Gunasekara; Chandima Jeewandara; Deshni Jayathilaka; Ananda Wijewickrama; Dinuka Guruge; Ruwan Wijayamuni; T.K. Tan; Graham S. Ogg; Alain Townsend; Gathsaurie Neelika Malavige. 2021. "Comparison of two assays to detect IgG antibodies to the receptor binding domain of SARS‑CoV‑2 as a surrogate marker for assessing neutralizing antibodies in COVID-19 patients." International Journal of Infectious Diseases 109, no. : 85-89.
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 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 Sri Lankan individuals. Methods: Paired nasopharangeal swabs were obtained from 4845 participants for validation of the SD-Biosensor rapid Ag assay and 3625 for the Abbott rapid Ag assay, in comparison to RT-qPCR. A short questionnaire was used to record symptoms at the time of testing, and blood samples were obtained from 2721 of them for detection of SARS-CoV-2 specific antibodies. Results: The overall sensitivity of the SD-Biosensor Ag kit was 36.5% and the Abbott Ag test was 50.76%. The Abbott Ag test showed specificity of 99.4% and the SD-Biosensor Ag test 97.5%. At Ct values 30 (46.1 to 82.9%). 32.1% of those who gave a positive result with the SD-Biosensor Ag test and 26.3% of those who gave positive results with the Abbott Ag test had SARS-CoV-2 antibodies at the time of detection. Conclusions: Both rapid Ag tests appeared to be highly sensitive in detecting individuals at lower Ct values, in a community setting in Sri Lanka, but it will be important to further establish the relationship to infectivity.
Chandima Jeewandara; Dinuka Guruge; Pradeep Pushpakumara; Deshan Madushanka; Tibutius Jayadas; Indika Chathuranga; Inoka Abeyratne; Saubhagya Danasekara; Thilagaraj Pathmanathan; Deshni Jayathilaka; Gayasha Somathilaka; Heshan Kuruppu; Laksiri Gomes; Vijith Gunasekara; Ruwan Wijayamuni; Graham Ogg; Gathsaurie Neelika Malavige. Sensitivity and Specificity of Two WHO Approved SARS-CoV2 Antigen Assays in Detecting Patients with SARS-CoV2 Infection. 2021, 1 .
AMA StyleChandima Jeewandara, Dinuka Guruge, Pradeep Pushpakumara, Deshan Madushanka, Tibutius Jayadas, Indika Chathuranga, Inoka Abeyratne, Saubhagya Danasekara, Thilagaraj Pathmanathan, Deshni Jayathilaka, Gayasha Somathilaka, Heshan Kuruppu, Laksiri Gomes, Vijith Gunasekara, Ruwan Wijayamuni, Graham Ogg, Gathsaurie Neelika Malavige. Sensitivity and Specificity of Two WHO Approved SARS-CoV2 Antigen Assays in Detecting Patients with SARS-CoV2 Infection. . 2021; ():1.
Chicago/Turabian StyleChandima Jeewandara; Dinuka Guruge; Pradeep Pushpakumara; Deshan Madushanka; Tibutius Jayadas; Indika Chathuranga; Inoka Abeyratne; Saubhagya Danasekara; Thilagaraj Pathmanathan; Deshni Jayathilaka; Gayasha Somathilaka; Heshan Kuruppu; Laksiri Gomes; Vijith Gunasekara; Ruwan Wijayamuni; Graham Ogg; Gathsaurie Neelika Malavige. 2021. "Sensitivity and Specificity of Two WHO Approved SARS-CoV2 Antigen Assays in Detecting Patients with SARS-CoV2 Infection." , no. : 1.
Cross-reactive T cell immunity to seasonal coronaviruses (HCoVs) may lead to immunopathology or protection during SARS-CoV2 infection. To understand the influence of cross-reactive T cell responses, we used IEDB (Immune epitope database) and NetMHCpan (ver. 4.1) to identify candidate CD8+ T cell epitopes, restricted through HLA-A and B alleles. Conservation analysis was carried out for these epitopes with HCoVs, OC43, HKU1, and NL63. 12/18 the candidate CD8+ T cell epitopes (binding score of ≥0.90), which had a high degree of homology (>75%) with the other three HCoVs were within the NSP12 and NSP13 proteins. They were predicted to be restricted through HLA-A*2402, HLA-A*201, HLA-A*206, and HLA-B alleles B*3501. Thirty-one candidate CD8+ T cell epitopes that were specific to SARS-CoV2 virus (<25% homology with other HCoVs) were predominantly identified within the structural proteins (spike, envelop, membrane, and nucleocapsid) and the NSP1, NSP2, and NSP3. They were predominantly restricted through HLA-B*3501 (6/31), HLA-B*4001 (6/31), HLA-B*4403 (7/31), and HLA-A*2402 (8/31). It would be crucial to understand T cell responses that associate with protection, and the differences in the functionality and phenotype of epitope specific T cell responses, presented through different HLA alleles common in different geographical groups, to understand disease pathogenesis.
Pradeep Pushpakumara; Deshan Madhusanka; Saubhagya Dhanasekara; Chandima Jeewandara; Graham Ogg; Gathsaurie Malavige. Identification of Novel Candidate CD8+ T Cell Epitopes of the SARS-CoV2 with Homology to Other Seasonal Coronaviruses. Viruses 2021, 13, 972 .
AMA StylePradeep Pushpakumara, Deshan Madhusanka, Saubhagya Dhanasekara, Chandima Jeewandara, Graham Ogg, Gathsaurie Malavige. Identification of Novel Candidate CD8+ T Cell Epitopes of the SARS-CoV2 with Homology to Other Seasonal Coronaviruses. Viruses. 2021; 13 (6):972.
Chicago/Turabian StylePradeep Pushpakumara; Deshan Madhusanka; Saubhagya Dhanasekara; Chandima Jeewandara; Graham Ogg; Gathsaurie Malavige. 2021. "Identification of Novel Candidate CD8+ T Cell Epitopes of the SARS-CoV2 with Homology to Other Seasonal Coronaviruses." Viruses 13, no. 6: 972.
Background Autoimmune encephalitis (AE) is now considered a main, potentially curable cause of encephalitis, but remains conspicuously underreported from South Asia. We studied the clinical characteristics in relation to their antibody status and outcomes of patients presenting with AE in Sri Lanka. Methods Patients admitting to government hospitals who were clinically suspected of AE by an on-site neurologist were prospectively recruited over a period of 12 months. Sera and cerebrospinal fluid were tested for NMDAR, AMPAR1, AMPAR2, LGI1, CASPR2, GABARB1/B2 antibodies (Ab) using commercial cell-based assays. Demographic, clinical and laboratory data were compiled into an investigator-administered proforma. Patients were reviewed at 1 year follow up either in person or via telephone. Results One-hundred and forty-two patients from 21 of 25 districts in Sri Lanka (median age = 20.5 years; range 1–86 years; females = 61.3%) were recruited. Of them, 65 (45.8%; median age = 19 years; range 1–86 years; females = 64.6%) fulfilled diagnostic criteria for probable NMDAR-antibody encephalitis (NMDARE) and 6 (4.2%; median age = 44 years; range 28–71 years; females = 83.3%) limbic encephalitis (LE). Abnormal behaviour (95.3%), seizures (81.5%) and movement disorders (69.2%) were the most frequent clinical manifestations of probable NMDARE. NMDAR-antibodies were detectable in 29 (44.6%) and not detectable in 36 in CSF of probable-NMDARE patients. Abnormal EEG was more frequent (p = 0.003) while a worse outcome (OR = 2.78; 95% CI = 0.88–9.09) and deaths (OR = 2.38; 95% CI = 0.67–8.33) were more likely in antibody-negative than antibody-positive probable-NMDARE. Most patients with LE had amnesia (50%) and/or confusion (100%) with agitation (83.3%) and seizures (100%) but none had detectable antibodies to any of the antigens tested. Conclusions NMDARE is the commonest type of AE among South Asians as is the case worldwide. Clinical presentations of NMDARAb-positive and NMDARAb-negative AE patients do not significantly differ but EEG may be a useful marker of an autoimmune basis for psychiatric symptoms.
Nilanka Wickramasinghe; Dhanushka Dasanayake; Neelika Malavige; Rajiva de Silva; Thashi Chang. Autoimmune encephalitis in a South Asian population. BMC Neurology 2021, 21, 1 -8.
AMA StyleNilanka Wickramasinghe, Dhanushka Dasanayake, Neelika Malavige, Rajiva de Silva, Thashi Chang. Autoimmune encephalitis in a South Asian population. BMC Neurology. 2021; 21 (1):1-8.
Chicago/Turabian StyleNilanka Wickramasinghe; Dhanushka Dasanayake; Neelika Malavige; Rajiva de Silva; Thashi Chang. 2021. "Autoimmune encephalitis in a South Asian population." BMC Neurology 21, no. 1: 1-8.
Background In order to understand the molecular epidemiology of 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 from 373 patients with COVID-19. Molecular clock phylogenetic analysis was undertaken to further explore dominant lineages. Results The B.1.411 lineage was most prevalent, which was established in Sri Lanka and caused outbreaks throughout the country until March 2021. The estimated time of the most recent common ancestor of this lineage was 29th June 2020 (95% lower and upper bounds 23rd May to 30th July), suggesting cryptic transmission may have occurred, prior to a large epidemic starting in October 2020. Returning travellers were identified with infections caused by lineage B.1.258, as well as the more transmissible B.1.1.7 lineage, which has replaced B.1.411 to fuel the ongoing large outbreak in the country. Conclusions The large outbreak that started in early October, is due to spread of a single virus lineage, B.1.411 until the end of March 2021, when B.1.1.7 emerged and became the dominant lineage.
Chandima Jeewandara; Deshni Jayathilaka; Diyanath Ranasinghe; Nienyun Sharon Hsu; Dinuka Ariyaratne; Tibutius Thanesh Jayadas; Deshan Madushanka; Benjamin B. Lindsey; Laksiri Gomes; Matthew D. Parker; Ananda Wijewickrama; Malika Karunaratne; Graham S. Ogg; Thushan I. de Silva; Gathsaurie Neelika Malavige. Genomic and epidemiological analysis of SARS-CoV-2 viruses in Sri Lanka. 2021, 1 .
AMA StyleChandima Jeewandara, Deshni Jayathilaka, Diyanath Ranasinghe, Nienyun Sharon Hsu, Dinuka Ariyaratne, Tibutius Thanesh Jayadas, Deshan Madushanka, Benjamin B. Lindsey, Laksiri Gomes, Matthew D. Parker, Ananda Wijewickrama, Malika Karunaratne, Graham S. Ogg, Thushan I. de Silva, Gathsaurie Neelika Malavige. Genomic and epidemiological analysis of SARS-CoV-2 viruses in Sri Lanka. . 2021; ():1.
Chicago/Turabian StyleChandima Jeewandara; Deshni Jayathilaka; Diyanath Ranasinghe; Nienyun Sharon Hsu; Dinuka Ariyaratne; Tibutius Thanesh Jayadas; Deshan Madushanka; Benjamin B. Lindsey; Laksiri Gomes; Matthew D. Parker; Ananda Wijewickrama; Malika Karunaratne; Graham S. Ogg; Thushan I. de Silva; Gathsaurie Neelika Malavige. 2021. "Genomic and epidemiological analysis of SARS-CoV-2 viruses in Sri Lanka." , no. : 1.
Background: In order to determine the immunogenicity of a single dose of the AZD1222/Covishield vaccine in a real-world situation, we assessed the immunogenicity, in a large cohort of health care workers in Sri Lanka. Methods: SARS-CoV-2 antibodies was carried out in 607 naive and 26 previously infected health care workers (HCWs) 28 to 32 days following a single dose of the vaccine. Haemagglutination test (HAT) for antibodies to the receptor binding domain (RBD) of the wild type virus, B.1.1.7, B.1.351 and the surrogate neutralization assay (sVNT) was carried out in 69 naive and 26 previously infected individuals. Spike protein (pools S1 and S2) specific T cell responses were measured by ex vivo ELISpot IFNg; assays in 76 individuals. Results: 92.9% of previously naive HCWs seroconverted to a single dose of the vaccine, irrespective of age and gender; and ACE2 blocking antibodies were detected in 67/69 (97.1%) previously naive vaccine recipients. Although high levels of antibodies were found to the RBD of the wild type virus, the titres for B.1.1.7 and B.1.351 were lower in previously naive HCWs. Ex vivo T cell responses were observed to S1 in 63.9% HCWs and S2 in 31.9%. The ACE2 blocking titres measured by the sVNT significantly increased (p<0.0001) from a median of 54.1 to 97.9 % of inhibition, in previously infected HCWs and antibodies to the RBD for the variants B.1.1.7 and B.1.351 also significantly increased. Discussion: a single dose of the AZD1222/Covishield vaccine was shown to be highly immunogenic in previously naive individuals inducing antibody levels greater than following natural infection. In infected individuals, a single dose induced very high levels of ACE2 blocking antibodies and antibodies to RBDs of SARS-CoV-2 variants of concern.
Chandima Jeewandara; Achala Kamaladasa; Pradeep Darshana Pushpakumara; Deshni Jayathilaka; Inoka Sepali; Saubhagyagya Danasekara; Dinuka Guruge; Thushali Ranasinghe; Shashika Dayarathne; Thilagaraj T Padmanadan; Gayasha Somathilaka; Deshan Madhusanka; Shyrar Tanussiya; Tibutius Jayadas; Heshan Kuruppu; Ayesha Wijesinghe; Nimasha Thashmi; Dushantha Milroy; Achini Nandasena; Nilanka Sanjeewani; Ruwan Wijayamuni; Sudath Samaraweera; Lisa Schimanski; Tiong Tan; Tao Dong; Graham S. Ogg; Alain Townsend; Gathsaurie Neelika Malavige. Antibody and T-cell responses to a single dose of the AZD1222/Covishield vaccine in previously SARS-CoV-2 infected and naive health care workers in Sri Lanka. 2021, 1 .
AMA StyleChandima Jeewandara, Achala Kamaladasa, Pradeep Darshana Pushpakumara, Deshni Jayathilaka, Inoka Sepali, Saubhagyagya Danasekara, Dinuka Guruge, Thushali Ranasinghe, Shashika Dayarathne, Thilagaraj T Padmanadan, Gayasha Somathilaka, Deshan Madhusanka, Shyrar Tanussiya, Tibutius Jayadas, Heshan Kuruppu, Ayesha Wijesinghe, Nimasha Thashmi, Dushantha Milroy, Achini Nandasena, Nilanka Sanjeewani, Ruwan Wijayamuni, Sudath Samaraweera, Lisa Schimanski, Tiong Tan, Tao Dong, Graham S. Ogg, Alain Townsend, Gathsaurie Neelika Malavige. Antibody and T-cell responses to a single dose of the AZD1222/Covishield vaccine in previously SARS-CoV-2 infected and naive health care workers in Sri Lanka. . 2021; ():1.
Chicago/Turabian StyleChandima Jeewandara; Achala Kamaladasa; Pradeep Darshana Pushpakumara; Deshni Jayathilaka; Inoka Sepali; Saubhagyagya Danasekara; Dinuka Guruge; Thushali Ranasinghe; Shashika Dayarathne; Thilagaraj T Padmanadan; Gayasha Somathilaka; Deshan Madhusanka; Shyrar Tanussiya; Tibutius Jayadas; Heshan Kuruppu; Ayesha Wijesinghe; Nimasha Thashmi; Dushantha Milroy; Achini Nandasena; Nilanka Sanjeewani; Ruwan Wijayamuni; Sudath Samaraweera; Lisa Schimanski; Tiong Tan; Tao Dong; Graham S. Ogg; Alain Townsend; Gathsaurie Neelika Malavige. 2021. "Antibody and T-cell responses to a single dose of the AZD1222/Covishield vaccine in previously SARS-CoV-2 infected and naive health care workers in Sri Lanka." , no. : 1.
Background Individuals who have not been exposed to the SARS-CoV2 virus have been shown to have T cells that respond to the virus, possibly due to the presence of cross-reactive T cell responses to other seasonal human coronaviruses (HCoVs). Such cross-reactive T cell immunity may lead to immunopathology or protection. Results To understand the influence of such cross-reactive T cell responses, we used IEDB (Immune epitope database) and NetMHCpan (ver. 4.1) to identify candidate CD8 + T cell epitopes, restricted through HLA-A and B alleles, which are seen in a frequency of > 10% in the Sri Lankan population. Conservation analysis was carried out for these candidate epitopes with the HCoVs, OC43, HKU1, NL63 and with the current circulating different variants of SARS-CoV2. 12/18 the candidate CD8 + T cell epitopes (binding score of ≥ 0.90), which had a high degree of homology (> 75%) with the other three HCoVs were within the NSP12 and NSP13 proteins. They were predicted to be restricted through HLA-A*2402, HLA-A*201, HLA-A*206 and HLA-B alleles B*3501. 31 candidate CD8 + T cell epitopes that were specific to SARS-CoV2 virus (< 25% homology with other HCoVs) were predominantly identified within the structural proteins (spike, envelop, membrane and nucleocapsid) and the NSP1, NSP2 and NSP3. They were predominantly restricted through HLA-B*3501 (6/31), HLA-B*4001 (6/31), HLA-B*4403(7/31) and HLA-A*2402 (8/31). The candidate CD8 + T cell epitopes that were homologous or were specific, with a binding score of ≥ 0.90, were found to be highly conserved within the SARS-CoV2 variants identified so far. Conclusions It would be crucial to understand T cell responses that associate with protection and the differences in the functionality and phenotype of epitope specific T cell responses, presented through different HLA alleles common in different geographical groups in order to understand disease pathogenesis.
Pradeep Pushpakumara; Deshan Madusanka; Saubhagyagya Danasekara; Chandima Jeewandara; Graham Ogg; Gathsaurie Neelika Malavige. Identification of novel candidate CD8+ T cell epitopes of the SARS-CoV2 with homology to other seasonal coronaviruses. 2021, 1 .
AMA StylePradeep Pushpakumara, Deshan Madusanka, Saubhagyagya Danasekara, Chandima Jeewandara, Graham Ogg, Gathsaurie Neelika Malavige. Identification of novel candidate CD8+ T cell epitopes of the SARS-CoV2 with homology to other seasonal coronaviruses. . 2021; ():1.
Chicago/Turabian StylePradeep Pushpakumara; Deshan Madusanka; Saubhagyagya Danasekara; Chandima Jeewandara; Graham Ogg; Gathsaurie Neelika Malavige. 2021. "Identification of novel candidate CD8+ T cell epitopes of the SARS-CoV2 with homology to other seasonal coronaviruses." , no. : 1.
Background Vascular leak is a hallmark of severe dengue, and high leukotriene levels have been observed in dengue mouse models, suggesting a role in disease pathogenesis. We sought to explore their role in acute dengue, by assessing levels of urinary LTE4 and urinary histamine in patients with varying severity of acute dengue. Methods Urinary LTE4, histamine and creatinine were measured by a quantitative ELISA, in healthy individuals (n = 19), patients with dengue fever (DF = 72) and dengue haemorrhagic fever DHF (n = 48). The kinetics of LTE4 and histamine and diurnal variations were assessed in a subset of patients. Results Urinary LTE4 levels were significantly higher (p = 0.004) in patients who proceed to develop DHF when compared to patients with DF during early illness (≤ 4 days) and during the critical phase (p = 0.02), which continued to rise in patients who developed DHF during the course of illness. However, LTE4 is unlikely to be a good biomarker as ROCs gave an AUC value of 0.67 (95% CI 0.57 and 0.76), which was nevertheless significant (p = 0.002). Urinary LTE4 levels did not associate with the degree of viraemia, infecting virus serotype and was not different in those with primary vs secondary dengue. Urinary histamine levels were significantly high in patients with acute dengue although no difference was observed between patients with DF and DHF and again did not associate with the viraemia. Interestingly, LTE4, histamine and the viral loads showed a marked diurnal variation in both patients with DF and DHF. Conclusions Our data suggest that LTE4 could play a role in disease pathogenesis and since there are safe and effective cysteinyl leukotriene receptor blockers, it would be important to assess their efficacy in reducing dengue disease severity.
Tehani Silva; Chandima Jeewandara; Laksiri Gomes; Chathurika Gangani; Sameera D. Mahapatuna; Thilagaraj Pathmanathan; Ananda Wijewickrama; Graham S. Ogg; Gathsaurie Neelika Malavige. Urinary leukotrienes and histamine in patients with varying severity of acute dengue. PLOS ONE 2021, 16, e0245926 .
AMA StyleTehani Silva, Chandima Jeewandara, Laksiri Gomes, Chathurika Gangani, Sameera D. Mahapatuna, Thilagaraj Pathmanathan, Ananda Wijewickrama, Graham S. Ogg, Gathsaurie Neelika Malavige. Urinary leukotrienes and histamine in patients with varying severity of acute dengue. PLOS ONE. 2021; 16 (2):e0245926.
Chicago/Turabian StyleTehani Silva; Chandima Jeewandara; Laksiri Gomes; Chathurika Gangani; Sameera D. Mahapatuna; Thilagaraj Pathmanathan; Ananda Wijewickrama; Graham S. Ogg; Gathsaurie Neelika Malavige. 2021. "Urinary leukotrienes and histamine in patients with varying severity of acute dengue." PLOS ONE 16, no. 2: e0245926.
In order to support vaccine development, and to aid convalescent plasma therapy, it would be important to understand the kinetics, timing and persistence of SARS-CoV-2 neutralizing antibodies (NAbs), and their association with clinical disease severity. Therefore, we used a surrogate viral neutralization test to evaluate their levels in patients with varying severity of illness, in those with prolonged shedding and those with mild/asymptomatic illness at various time points. Patients with severe or moderate COVID-19 illness had earlier appearance of NAbs at higher levels compared to those with mild or asymptomatic illness. Furthermore, those who had prolonged shedding of the virus, had NAbs appearing faster and at higher levels than those who cleared the virus earlier. During the first week of illness the NAb levels of those with mild illness was significantly less (p = 0.01), compared to those with moderate and severe illness. At the end of 4 weeks (28 days), although 89% had NAbs, 38/76 (50%) in those with > 90 days had a negative result for the presence of NAbs. The Ab levels significantly declined during convalescence (> 90 days since onset of illness), compared to 4 to 8 weeks since onset of illness. Our data show that high levels of NAbs during early illness associated with clinical disease severity and that these antibodies declined in 50% of individuals after 3 months since onset of illness.
Chandima Jeewandara; Deshni Jayathilaka; Laksiri Gomes; Ananda Wijewickrama; Eranga Narangoda; Damayanthi Idampitiya; Dinuka Guruge; Ruwan Wijayamuni; Suranga Manilgama; Graham S. Ogg; Chee Wah Tan; Lin-Fa Wang; Gathsaurie Neelika Malavige. SARS-CoV-2 neutralizing antibodies in patients with varying severity of acute COVID-19 illness. Scientific Reports 2021, 11, 1 -7.
AMA StyleChandima Jeewandara, Deshni Jayathilaka, Laksiri Gomes, Ananda Wijewickrama, Eranga Narangoda, Damayanthi Idampitiya, Dinuka Guruge, Ruwan Wijayamuni, Suranga Manilgama, Graham S. Ogg, Chee Wah Tan, Lin-Fa Wang, Gathsaurie Neelika Malavige. SARS-CoV-2 neutralizing antibodies in patients with varying severity of acute COVID-19 illness. Scientific Reports. 2021; 11 (1):1-7.
Chicago/Turabian StyleChandima Jeewandara; Deshni Jayathilaka; Laksiri Gomes; Ananda Wijewickrama; Eranga Narangoda; Damayanthi Idampitiya; Dinuka Guruge; Ruwan Wijayamuni; Suranga Manilgama; Graham S. Ogg; Chee Wah Tan; Lin-Fa Wang; Gathsaurie Neelika Malavige. 2021. "SARS-CoV-2 neutralizing antibodies in patients with varying severity of acute COVID-19 illness." Scientific Reports 11, no. 1: 1-7.
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 of COVID-19 and acute dengue at different time points of illness. During early disease, patients who proceeded to develop COVID-19 severe pneumonia (SP) and DHF had significantly higher levels of IL-6, IL-10 and MIP3α than those who developed mild illness. The lowest levels of IFNγ in early illness were seen in those who succumbed to their illness due to COVID-19. Levels of serum IL-10 (p = 0.0001), IL-6 (p = 0.002), MIP-3α (p = 0.02) and CD40-L levels (p = 0.002) significantly increased from 5 to 9 day of illness to 10–21 day of illness in patients with moderate-to-severe COVID-19, but not in those with mild illness. In contrast, these cytokine/chemokine levels remained unchanged in those with DHF or dengue fever (DF) during febrile and critical phases. Although IL-10 levels were significantly higher in COVID-19 patients with SP, patients with DHF had 25-fold higher levels, whereas IL-6 levels were 11-fold higher in those with COVID-19 SP. IL-10 and other cytokines were evaluated in a larger cohort of patients during early illness (≤ 4 days) who proceeded to develop DF (n = 71) or DHF (n = 64). Of the cytokines evaluated, IL-10 was significantly higher (p < 0.0001) in those who went on to develop DHF compared to DF. Low IFNγ response to the SARS-CoV2 and high levels of immunosuppressive IL-10 in both COVID-19 and dengue during early illness are indicators of an altered antiviral response potentially contributing to disease severity.
Shashika Dayarathna; Chandima Jeewandara; Laksiri Gomes; Gayasha Somathilaka; Deshni Jayathilaka; Vimalahan Vimalachandran; Ananda Wijewickrama; Eranga Narangoda; Damayanthi Idampitiya; Graham S. Ogg; Gathsaurie Neelika Malavige. Similarities and differences between the ‘cytokine storms’ in acute dengue and COVID-19. Scientific Reports 2020, 10, 1 -12.
AMA StyleShashika Dayarathna, Chandima Jeewandara, Laksiri Gomes, Gayasha Somathilaka, Deshni Jayathilaka, Vimalahan Vimalachandran, Ananda Wijewickrama, Eranga Narangoda, Damayanthi Idampitiya, Graham S. Ogg, Gathsaurie Neelika Malavige. Similarities and differences between the ‘cytokine storms’ in acute dengue and COVID-19. Scientific Reports. 2020; 10 (1):1-12.
Chicago/Turabian StyleShashika Dayarathna; Chandima Jeewandara; Laksiri Gomes; Gayasha Somathilaka; Deshni Jayathilaka; Vimalahan Vimalachandran; Ananda Wijewickrama; Eranga Narangoda; Damayanthi Idampitiya; Graham S. Ogg; Gathsaurie Neelika Malavige. 2020. "Similarities and differences between the ‘cytokine storms’ in acute dengue and COVID-19." Scientific Reports 10, no. 1: 1-12.
Although serum lipopolysaccharide (LPS) was shown to associate with development of severe dengue, the reasons for high LPS and its subsequent involvement in disease pathogenesis are not known. We assessed serum LPS, C-reactive protein (CRP), and procalcitonin in patients with acute dengue fever (DF = 129) and dengue haemorrhagic fever (DHF = 64) and correlated these observations with the presence of comorbid illnesses, and clinical disease severity. Serum LPS levels were significantly (p = 0.01) higher in patients with DHF, compared to those with DF. In total, 45 (70%) of those with DHF and 63 (49%) of those with DF had detectable LPS and therefore, the presence of LPS was significantly associated with DHF (p = 0.005, OR = 2.48, 95% CI: 1.29 to 4.64). Those with metabolic diseases, 22/29 (75.9%) and those with atopic diseases 17/22 (77.3%) were significantly more likely to have detectable LPS levels (p = 0.025, OR = 2.9, 95% CI-1.17 to 7.59 and p = 0.039, OR = 3.06, 95% CI-1.07 to 7.81 respectively). Those with detectable LPS levels were also more likely to develop shock and severe thrombocytopenia. Patients with detectable LPS were more likely to have elevated CRP levels and were more likely to develop DHF. Procalcitonin levels too were significantly (p = 0.009) higher in those with DHF compared to those with DF and were more likely to be high in those with detectable serum LPS. Since serum LPS levels were higher in patients with DHF and significantly more likely to be present in those with comorbid illnesses, the possible role of LPS in disease pathogenesis should be further investigated.
N. L. Ajantha Shyamali; Sameera D. Mahapatuna; Laksiri Gomes; Ananda Wijewickrama; Graham S. Ogg; Gathsaurie Neelika Malavige. Risk Factors for Elevated Serum Lipopolysaccharide in Acute Dengue and Association with Clinical Disease Severity. Tropical Medicine and Infectious Disease 2020, 5, 170 .
AMA StyleN. L. Ajantha Shyamali, Sameera D. Mahapatuna, Laksiri Gomes, Ananda Wijewickrama, Graham S. Ogg, Gathsaurie Neelika Malavige. Risk Factors for Elevated Serum Lipopolysaccharide in Acute Dengue and Association with Clinical Disease Severity. Tropical Medicine and Infectious Disease. 2020; 5 (4):170.
Chicago/Turabian StyleN. L. Ajantha Shyamali; Sameera D. Mahapatuna; Laksiri Gomes; Ananda Wijewickrama; Graham S. Ogg; Gathsaurie Neelika Malavige. 2020. "Risk Factors for Elevated Serum Lipopolysaccharide in Acute Dengue and Association with Clinical Disease Severity." Tropical Medicine and Infectious Disease 5, no. 4: 170.
Although immune responses to the Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) have a potential to modulate the immune responses to each other, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV specific, DENV non cross-reactive antibody responses by identifying JEV specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV specific antibodies associate with dengue disease severity. 22 JEV specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed in individuals who were non-immune to JEV and DENV (JEV-DENV-, N = 30), those who were only immune to the JEV and not DENV (JEV+DENV-, N = 30), those who were only immune to DENV(JEV-DENV+, N = 30) and in those who were immune to both viruses (JEV+DENV+, N = 30). 7/22 peptides were found to be highly immunogenic and specific and these 7 peptides were used as a pool to further evaluate JEV-specific responses. All 30/30 JEV+DENV- and 30/30 JEV+DENV+ individuals, and only 3/30 (10%) JEV-DENV+ individuals responded to this pool. We further evaluated this pool of 7 peptides in patients following primary and secondary dengue infection during the convalescent period and found that the JEV-specific peptides, were unlikely to cross react with DENV IgG antibodies. We further compared this in-house ELISA developed with the peptide pool with an existing commercial JEV IgG assay to identify JEV-specific IgG following vaccination, and our in-house ELISA was found to be more sensitive. We then proceeded to investigate if the presence of JEV-specific antibodies were associated with dengue disease severity, and we found that those who had past severe dengue (n = 175) were significantly more likely (p<0.0001) to have JEV-specific antibodies than those with past non-severe dengue (n = 175) (OR 5.3, 95% CI 3.3 to 8.3). As our data show that this assay is highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.
Pradeep Darshana Pushpakumara; Chandima Jeewandara; Laksiri Gomes; Yashodha Perera; Ananda Wijewickrama; Gathsaurie Neelika Malavige; Charitha Goonesekara. Development and validation of an assay for detection of Japanese encephalitis virus specific antibody responses. PLOS ONE 2020, 15, e0238609 .
AMA StylePradeep Darshana Pushpakumara, Chandima Jeewandara, Laksiri Gomes, Yashodha Perera, Ananda Wijewickrama, Gathsaurie Neelika Malavige, Charitha Goonesekara. Development and validation of an assay for detection of Japanese encephalitis virus specific antibody responses. PLOS ONE. 2020; 15 (10):e0238609.
Chicago/Turabian StylePradeep Darshana Pushpakumara; Chandima Jeewandara; Laksiri Gomes; Yashodha Perera; Ananda Wijewickrama; Gathsaurie Neelika Malavige; Charitha Goonesekara. 2020. "Development and validation of an assay for detection of Japanese encephalitis virus specific antibody responses." PLOS ONE 15, no. 10: e0238609.
In order to support vaccine development, and to aid convalescent plasma therapy, it would be important to understand the kinetics, timing and persistence of SARS-CoV2 neutralizing antibodies (NAbs), and their association with clinical disease severity. Therefore, we used a surrogate viral neutralization test to evaluate their levels in patients with varying severity of illness, in those with prolonged shedding and those with mild/asymptomatic illness at various time points.Patients with severe or moderate COVID-19 illness had earlier appearance of NAbs at higher levels compared to those with mild or asymptomatic illness. Furthermore, those who had prolonged shedding of the virus, had NAbs appearing faster and at higher levels than those who cleared the virus earlier. During the first week of illness the NAb levels of those with mild illness was significantly less (p=0.01), compared to those with moderate and severe illness. At the end of 4 weeks (28 days), although 89% had Nabs, 38/76 (50%) in those with >90 days had a negative result for the presence of NAbs. The Ab levels significantly declined during convalescence (>90 days since onset of illness), compared to 4 to 8 weeks since onset of illness. Our data show that high levels of NAbs during early illness associated with clinical disease severity and that these antibodies declined in 50% of individuals after 3 months since onset of illness.
Chandima Jeewandara; Deshni Jayathilaka; Laksiri Gomes; Ananda Wijewickrama; Eranga Narangoda; Damayanthi Idampitiya; Dinuka Guruge; Ruwan Wijayamuni; Suranga Manilgama; Graham Ogg; Chee Wah Tan; Lin-Fa Wang; Gathsaurie Neelika Malavige. SARS-CoV-2 neutralizing antibodies in patients with varying severity of acute COVID-19 illness. 2020, 1 .
AMA StyleChandima Jeewandara, Deshni Jayathilaka, Laksiri Gomes, Ananda Wijewickrama, Eranga Narangoda, Damayanthi Idampitiya, Dinuka Guruge, Ruwan Wijayamuni, Suranga Manilgama, Graham Ogg, Chee Wah Tan, Lin-Fa Wang, Gathsaurie Neelika Malavige. SARS-CoV-2 neutralizing antibodies in patients with varying severity of acute COVID-19 illness. . 2020; ():1.
Chicago/Turabian StyleChandima Jeewandara; Deshni Jayathilaka; Laksiri Gomes; Ananda Wijewickrama; Eranga Narangoda; Damayanthi Idampitiya; Dinuka Guruge; Ruwan Wijayamuni; Suranga Manilgama; Graham Ogg; Chee Wah Tan; Lin-Fa Wang; Gathsaurie Neelika Malavige. 2020. "SARS-CoV-2 neutralizing antibodies in patients with varying severity of acute COVID-19 illness." , no. : 1.
Although infection with the dengue virus (DENV) causes severe dengue, it causes a mild self-limiting illness in the majority of individuals. There is emerging evidence that an aberrant immune response in the initial stages of infection lead to severe disease. Many inflammatory cytokines, chemokines, and lipid mediators are significantly higher in patients with severe dengue compared to those who develop mild infection, during febrile phase of illness. Monocytes, mast cells, and many other cells of the immune system, when infected with the DENV, especially in the presence of poorly neutralizing antibodies, leads to production of pro-inflammatory cytokines and inhibition of interferon signaling pathways. In addition, production of immunosuppressive cytokines such as IL-10 further leads to inhibition of cellular antiviral responses. This dysregulated and aberrant immune response leads to reduced clearance of the virus, and severe dengue by inducing a vascular leak and excessive inflammation due to high levels of inflammatory cytokines. Individuals with comorbid illnesses could be prone to more severe dengue due to low grade endotoxemia, gut microbial dysbiosis and an altered phenotype of innate immune cells. The immunosuppressive and inflammatory lipid mediators and altered phenotype of monocytes are likely to further act on T cells and B cells leading to an impaired adaptive immune response to the virus. Therefore, in order to identify therapeutic targets for treatment of dengue, it would be important to further characterize these mechanisms in order for early intervention. In this review, we discuss the differences in the innate immune responses in those who progress to develop severe dengue, compared to those with milder disease in order to understand the mechanisms that lead to severe dengue.
Gathsaurie Neelika Malavige; Chandima Jeewandara; Graham S. Ogg. Dysfunctional Innate Immune Responses and Severe Dengue. Frontiers in Cellular and Infection Microbiology 2020, 10, 590004 .
AMA StyleGathsaurie Neelika Malavige, Chandima Jeewandara, Graham S. Ogg. Dysfunctional Innate Immune Responses and Severe Dengue. Frontiers in Cellular and Infection Microbiology. 2020; 10 ():590004.
Chicago/Turabian StyleGathsaurie Neelika Malavige; Chandima Jeewandara; Graham S. Ogg. 2020. "Dysfunctional Innate Immune Responses and Severe Dengue." Frontiers in Cellular and Infection Microbiology 10, no. : 590004.