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Article: Pathogenesis of severe dengue infection.

Malavige, G N / Ogg, G

2012 Volume 57, Issue 3, Page(s) 97–100

MeSH term(s)	Humans ; Severe Dengue/epidemiology ; Severe Dengue/etiology ; Sri Lanka/epidemiology
Language	English
Publishing date	2012-10-21
Publishing country	Sri Lanka
Document type	Journal Article
ZDB-ID	419365-9
ISSN	0009-0875
ISSN	0009-0875
DOI	10.4038/cmj.v57i3.4701
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Article ; Online: Mathematical Modelling of Immune Parameters in the Evolution of Severe Dengue.

Premaratne, M K / Perera, S S N / Malavige, G N / Jayasinghe, Saroj

Computational and mathematical methods in medicine

2017 Volume 2017, Page(s) 2187390

Abstract: ... ...

Abstract	Aims
MeSH term(s)	Algorithms ; Databases, Factual ; Dengue/blood ; Dengue/epidemiology ; Dengue/immunology ; Dengue Virus ; Disease Outbreaks ; Fuzzy Logic ; Humans ; Immunoglobulin G/chemistry ; Lymphocyte Count ; Medical Informatics ; Models, Theoretical ; Multivariate Analysis ; Platelet Count ; Reproducibility of Results ; Severe Dengue/blood ; Severe Dengue/epidemiology ; Severe Dengue/immunology ; Time Factors ; Viral Nonstructural Proteins/metabolism
Chemical Substances	Immunoglobulin G ; NS1 protein, dengue-1 virus ; Viral Nonstructural Proteins
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ZDB-ID	2252430-7
ISSN	1748-6718 ; 1748-670X ; 1027-3662
ISSN (online)	1748-6718
ISSN	1748-670X ; 1027-3662
DOI	10.1155/2017/2187390
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Article ; Online: Antibody and memory B cell responses to the dengue virus NS1 antigen in individuals with varying severity of past infection.

Ramu, Shyrar Tanussiya / Dissanayake, Madushika / Jeewandara, Chandima / Bary, Farha / Harvie, Michael / Gomes, Laksiri / Wijesinghe, Ayesha / Ariyaratne, Dinuka / Ogg, Graham S / Malavige, Gathsaurie Neelika

Immunology

2023 Volume 170, Issue 1, Page(s) 47–59

Abstract: ... to assess NS1-Abs and NS1-Ab subclasses for all four DENV serotypes in individuals with past DF (n = 22 ... those with past DHF (n = 14) and seronegative (SN) individuals (n = 7). B-cell ELISpot assays were used to assess ...

Abstract	To further understand the role of NS1-specific antibodies (Abs) in disease pathogenesis, we compared neutralizing antibody levels (Nabs), NS1-Ab levels, IgG antibody subclass profiles and NS1-specific memory B-cell responses (Bmems) in individuals, with varying severity of past dengue. Nabs (Neut50 titres) were assessed using the Foci Reduction Neutralization Test (FRNT) and in-house ELISAs were used to assess NS1-Abs and NS1-Ab subclasses for all four DENV serotypes in individuals with past DF (n = 22), those with past DHF (n = 14) and seronegative (SN) individuals (n = 7). B-cell ELISpot assays were used to assess NS1-specific Bmem responses. 15/22 (68.18%) individuals with past DF and 9/14 (64.29%) individuals with past DHF had heterotypic infections. Neut50 titres were found to be significantly higher for DENV1 than DENV2 (p = 0.0006) and DENV4 (p = 0.0127), in those with past DHF, whereas there was no significant difference seen in titres for different DENV serotypes in those with past DF. Overall NS1-Ab to all serotypes and NS1-specific IgG1 responses for DENV1, 2 and 4 serotypes were significantly higher in those with past DHF than individuals with past DF. Those with past DHF also had higher IgG1 than IgG3 for DENV1 and DENV3, whereas no differences were seen in those with past DF. Over 50% of those with past DF or DHF had NS1-specific Bmem responses to >2 DENV serotypes. There was no difference in the frequency of Bmem responses to any of the DENV serotypes between individuals with past DF and DHF. Although the frequency of Bmem responses to DENV1 correlated with DENV1-specific NS1-Abs levels (Spearman r = 0.35, p = 0.02), there was no correlation with other DENV serotypes. We found that those with past DF had broadly cross-reactive Nabs, while those with past DHF had higher NS1-Ab responses possibly with a different functionality profile than those with past DF. Therefore, it would be important to further evaluate the functionality of NS1-specific antibody and Bmem responses to find out the type of antibody repertoire that is associated with protection against severe disease.
MeSH term(s)	Humans ; Dengue Virus ; Dengue ; Antibodies, Viral ; Memory B Cells ; Antibodies, Neutralizing ; Immunoglobulin G ; Broadly Neutralizing Antibodies
Chemical Substances	Antibodies, Viral ; Antibodies, Neutralizing ; Immunoglobulin G ; Broadly Neutralizing Antibodies
Language	English
Publishing date	2023-04-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.13651
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Article: Doctors, drug companies and medical ethics: a Sri Lankan perspective.

Malavige, G N

Indian journal of medical ethics

2004 Volume 1, Issue 1, Page(s) 26

MeSH term(s)	Developing Countries ; Drug Industry/economics ; Drug Industry/ethics ; Education, Medical, Continuing/economics ; Ethics, Medical ; Humans ; Interprofessional Relations/ethics ; Physicians/economics ; Physicians/ethics ; Sri Lanka
Language	English
Publishing date	2004-01
Publishing country	India
Document type	Journal Article
ISSN	0974-8466
ISSN	0974-8466
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Article ; Online: Chronic cough. . . .and tropical pulmonary eosinophilia.

Malavige, G N

BMJ (Clinical research ed.)

2003 Volume 326, Issue 7397, Page(s) 1036

MeSH term(s)	Chronic Disease ; Cough/etiology ; Humans ; Pulmonary Eosinophilia/complications
Language	English
Publishing date	2003-05-10
Publishing country	England
Document type	Comment ; Letter
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
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Article: Does leptin resistance contribute to infections in patients with diabetes?

Malavige, G N

Molecular pathology : MP

2003 Volume 56, Issue 4, Page(s) 248

MeSH term(s)	Communicable Diseases/immunology ; Communicable Diseases/metabolism ; Diabetes Mellitus/metabolism ; Diabetes Mellitus/microbiology ; Disease Susceptibility ; Humans ; Leptin/metabolism
Chemical Substances	Leptin
Language	English
Publishing date	2003-07-17
Publishing country	England
Document type	Letter
ZDB-ID	1363384-3
ISSN	1472-4154 ; 1366-8714 ; 1355-2910
ISSN (online)	1472-4154
ISSN	1366-8714 ; 1355-2910
DOI	10.1136/mp.56.4.248-a
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Article ; Online: Altered monocyte response to the dengue virus in those with varying severity of past dengue infection.

Kamaladasa, Achala / Gomes, Laksiri / Wijesinghe, Ayesha / Jeewandara, Chandima / Toh, Ying Xiu / Jayathilaka, Deshni / Ogg, Graham S / Fink, Katja / Malavige, G N

Antiviral research

2019 Volume 169, Page(s) 104554

Abstract: ... SD (n = 6) or past NSD (n = 6) were infected at MOI one with all four DENV serotypes following ...

Abstract	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 at MOI one with all four DENV serotypes following incubation with autologous serum. 36-hours post infection, levels of inflammatory cytokines and viral loads were measured in the supernatant and expression of genes involved in viral sensing and interferon signaling was determined. Results: Monocytes of individuals with past SD produced significantly higher viral loads (p = 0.0426 and cytokines (IL-10 p = 0.008, IL-1β p = 0.008 and IL-6 p = 0.0411) when infected with DENV serotypes they were not immune to, compared to those who has past NSD. Monocytes of individuals with past SD also produced significantly higher viral loads (p = 0.022) and cytokines (IL-10 p < 0.0001, IL-1β < 0.0001 and IL-6 p < 0.0001) when infected with DENV serotypes they were previously exposed to, despite the monocytes being infected in the presence of autologous serum. A significant upregulation of NLRP3 (p = 0.005), RIG-I (0.0004) and IFNB-1 (0.01) genes were observed in those who had past SD compared to past NSD when infected with non-immune DENV serotypes. Conclusion: Monocytes from those with past SD appear to show marked differences in viral loads, viral sensing and production of inflammatory mediators in response to the DENV, when compared to those who experienced past NSD, suggesting that initial innate immune responses may influence the disease outcome.
MeSH term(s)	Antibodies, Viral ; Cytokines/blood ; Cytokines/genetics ; Dengue/immunology ; Dengue/virology ; Dengue Virus/classification ; Dengue Virus/immunology ; Dengue Virus/physiology ; Gene Expression ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Immunity ; Interleukin-10/blood ; Interleukin-1beta/blood ; Interleukin-6/blood ; Monocytes/immunology ; Monocytes/virology ; Serogroup ; Viral Load
Chemical Substances	Antibodies, Viral ; Cytokines ; IL10 protein, human ; IL1B protein, human ; Interleukin-1beta ; Interleukin-6 ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2019-07-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2019.104554
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Article ; Online: Comparison of the kinetics and magnitude of antibody responses to different SARS-CoV-2 proteins in Sinopharm/BBIBP-CorV vaccinees following the BNT162b2 booster or natural infection.

Jeewandara, Chandima / Aberathna, Inoka Sepali / Dayarathna, Shashika / Nimasha, Thashmi / Ranasinghe, Thushali / Jayamali, Jeewantha / Kamaladasa, Achala / Karunanada, Maneshka / Perera, Lahiru / Ogg, Graham S / Malavige, Gathsaurie Neelika

PloS one

2022 Volume 17, Issue 10, Page(s) e0274845

Abstract: ... infected (n = 20) and uninfected (n = 20) Sinopharm/BBIBP-CorV vaccinees. The IgG antibodies to the S, S1 ... and S2 and N were several folds higher in those who had natural infection compared to uninfected ... vaccinees at 7 months post second dose, including those who remained uninfected and not boosted (n = 21), or ...

Abstract	The kinetics and magnitude of antibody responses to different proteins of the SARS-CoV-2 virus in Sinopharm/BBIBP-CorV vaccinees has not been previously studied. Therefore, we investigated antibody responses to different SARS-CoV-2 proteins at 2 weeks, 3 months, and 6 months post-second dose in previously infected (n = 20) and uninfected (n = 20) Sinopharm/BBIBP-CorV vaccinees. The IgG antibodies to the S, S1 and S2 and N were several folds higher in those who had natural infection compared to uninfected individuals at all time points. We then compared the persistence of antibody responses and effect of natural omicron infection or BNT162b2 booster in Sinopharm/BBIBP-CorV vaccinees. We measured the total antibodies to the RBD, ACE2 blocking antibodies and antibody responses to different SARS-CoV-2 proteins in Sinopharm vaccinees at 7 months post second dose, including those who remained uninfected and not boosted (n = 21), or those who had previous infection and who did not obtain the booster (n = 17), those who were not infected, but who received a BNT162b2 booster (n = 30), or those who did not receive the booster but were infected with omicron (n = 29). At 7 months post second dose uninfected (no booster) had the lowest antibody levels to the RBD, while omicron infected vaccinees showed significantly higher anti-RBD antibody levels (p = 0.04) than vaccinees who received the booster. Only 3/21 cohort A (14.3%) had ACE2 blocking antibodies, while higher frequencies were observed in naturally infected individuals (100%), those who received the booster (18/21, 85.7%), and omicron infected individuals (100%). Pre-vaccination, naturally infected had the highest antibody levels to the N protein. These data suggest that those previously infected Sinopharm/BBIBP-CorV vaccinees have a robust antibody response, 7 months post vaccination, while vaccinees who were naturally infected with omicron had a similar immune response to those who received the booster. It will be important to investigate implications for subsequent clinical protection.
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Antibodies, Blocking ; Antibodies, Viral ; Antibody Formation ; BNT162 Vaccine ; COVID-19 ; Humans ; Immunoglobulin G ; SARS-CoV-2
Chemical Substances	Antibodies, Blocking ; Antibodies, Viral ; Immunoglobulin G ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-10-13
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0274845
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Article ; Online: Development and validation of an assay for detection of Japanese encephalitis virus specific antibody responses.

Pushpakumara, Pradeep Darshana / Jeewandara, Chandima / Gomes, Laksiri / Perera, Yashodha / Wijewickrama, Ananda / Malavige, Gathsaurie Neelika / Goonesekara, Charitha

PloS one

2020 Volume 15, Issue 10, Page(s) e0238609

Abstract: ... 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 ... severity, and we found that those who had past severe dengue (n = 175) were significantly more likely (p<0 ...

Abstract	Introduction: 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. Methodology and results: 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). Conclusions: 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.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Amino Acid Sequence ; Antibodies, Viral/blood ; Antibody Specificity ; Child ; Conserved Sequence ; Cross Reactions ; Dengue/immunology ; Dengue/virology ; Dengue Virus/classification ; Dengue Virus/genetics ; Dengue Virus/immunology ; Encephalitis Virus, Japanese/genetics ; Encephalitis Virus, Japanese/immunology ; Encephalitis, Japanese/epidemiology ; Encephalitis, Japanese/immunology ; Encephalitis, Japanese/virology ; Enzyme-Linked Immunosorbent Assay/methods ; Enzyme-Linked Immunosorbent Assay/statistics & numerical data ; Female ; Healthy Volunteers ; Humans ; Immunoglobulin G/blood ; Male ; Middle Aged ; Peptide Fragments/genetics ; Peptide Fragments/immunology ; Sensitivity and Specificity ; Seroepidemiologic Studies ; Serogroup ; Sri Lanka/epidemiology ; Vaccination ; Viral Proteins/genetics ; Viral Proteins/immunology ; Young Adult
Chemical Substances	Antibodies, Viral ; Immunoglobulin G ; Peptide Fragments ; Viral Proteins
Language	English
Publishing date	2020-10-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Validation Study
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0238609
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Article ; Online: Antibody responses to Sinopharm/BBIBP-CorV in pregnant mothers in Sri Lanka.

Jeewandara, Chandima / Jayampathi, K A Chintha S / Ranasinghe, Thushali / Aberathna, Inoka Sepali / Gunasekara, Banuri / Danasekara, Saubhagya / Nimasha, Thashmi / Kuruppu, Heshan / Dissanayake, Osanda / Gamalath, Nayanathara / Ekanayake, Dinithi / Jayamali, Jewantha / Somathilake, Gayasha / Guruge, Dinuka / Wijayamuni, Ruwan / Kamaladasa, Achala / Ogg, Graham S / Malavige, Gathsaurie Neelika

PLOS global public health

2022 Volume 2, Issue 7, Page(s) e0000607

Abstract: ... measured by ELISA in pregnant mothers (n = 94) who received the vaccine in the first (n = 2), second (n ... 57) and third (n = 33) trimester of pregnancy. Data regarding adverse events and fetal and maternal ...

Abstract	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 total antibodies and ACE2 blocking antibodies were measured by ELISA in pregnant mothers (n = 94) who received the vaccine in the first (n = 2), second (n = 57) and third (n = 33) trimester of pregnancy. Data regarding adverse events and fetal and maternal outcomes were obtained from the women once they delivered. No adverse maternal or fetal complications reported such as miscarriage, thrombotic events, hypertensive disorders, fetal death, preterm delivery, or congenital anomalies were reported. 58/94 (61.7%) had RBD binding antibodies and were found to be seropositive at the time of recruitment. All women seroconverted after the second dose and 31/36 previously uninfected women and 57/58 previously infected women gave a positive response to ACE2 blocking antibodies. The RBD binding antibody levels (p = 0.0002) and ACE2 blocking antibodies (p<0.0001) were significantly higher in previously infected individuals post-second dose compared to uninfected individuals. Conclusions: The Sinopharm/ BBIBP-CorV vaccine appeared safe and induced high seroconversion rates and ACE2 blocking antibodies in pregnant mothers in the second and third trimester in pregnancy. However, the RBD binding antibodies and ACE2 blocking antibodies post-second dose were significantly higher in previously infected pregnant mothers post-second dose, suggesting that two doses of the vaccine are likely to be less immunogenic in previously unexposed individuals.
Language	English
Publishing date	2022-07-18
Publishing country	United States
Document type	Journal Article
ISSN	2767-3375
ISSN (online)	2767-3375
DOI	10.1371/journal.pgph.0000607
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