Browsing by Author "Gunasekera, D."

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Comparison of urban diabetics with optimal and suboptimal control
(British Medical Association, London, 2011) Pinidiyapathirage, M.; Warnakulasuriya, T.; Kasturiratne, A.; Ranawaka, U.; Gunasekera, D.; Wijekoon, N.; Medagoda, K.; Perera, S.; Takeuchi, F.; Kato, N.; Wickremasinghe, A.R.
Introduction The prevalence of Diabetes Mellitus in Sri Lanka is increasing. We describe the characteristics of patients with optimal and suboptimal control of diabetes among known diabetics in a 35–64-year-old urban population resident in the Ragama Medical Officer of Health (Ragama MOH) area of Sri Lanka. Methods A cross sectional study was conducted among 2986 randomly selected 35–64 year olds in the Ragama MOH area from January to September 2007. A detailed history was taken and participants were subjected to a physical examination and assay of fasting blood glucose and HbA1C. A HBA1C <6.5 was taken as evidence of optimal control. Results There were 474 persons (194 males and 280 females) who gave a past history of diabetes. 9 males and 9 females were not on any treatment. 27 persons (9 males and 18 females) were on insulin. Of the 474 diabetics, 113 (48 males and 65 females) had a HbA1c <6.5. The average fasting blood glucose of diabetics with optimal control was 120+21 mg/dl. The mean fasting blood glucose level of the 361 subjects with sub optimal control was 190+70 mg/dl. Optimal glycaemic control was not associated with alcohol intake, smoking, obesity, central obesity and low physical activity levels. Conclusions Most known diabetics had access to treatment but only approximately 25% were optimally treated. The need to optimally manage these patients is highlighted.
Correlates of serum homocysteine in a Sri Lankan population
(American Association For Clinical Chemistry, 2010) Chackrewarthy, S.; Wijayasinghe, Y.S.; Gunasekera, D.; Wickremasinghe, R.; Kato, N.
Correlates of total serum homocysteine concentration in a Sri Lankan population BACKGROUND: Hyperhomocysteinemia, a possible risk factor for vascular disease occurs at a higher prevalence in South Asian countries. Serum homocysteine concentrations are influenced by genetic, nutritional and lifestyle factors. Correlates of total serum homocysteine concentration (tHcy) are not well characterized in the Sri Lankan population. Such information is important in developing therapeutic and preventative strategies. OBJECTIVE: To investigate the factors potentially associated with fasting levels of serum tHcy in a Sri Lankan population. METHODS: In a cross sectional study, 177 apparently healthy volunteers (91 men and 86 women) aged 38-65 years were selected from residents in an urban health administrative area. Individuals with a history of chronic disease and with any pharmacological treatment were excluded from the study. Information on diet, lifestyle factors and medical history were recorded. Anthropometric indices and blood pressure were measured according standard protocols. Fasting serum levels of tHcy, insulin, creatinine, folate and lipids were estimated using standard protocols. RESULTS: Fasting serum tHcy levels were higher in males than in females (geometric mean +/- SD, 13.75 mumol/l +/- 1.41 Vs. 9.58 mumol/l +/- 1.43, p<0.001) and were positively associated with age (r=0.204, p< 0.01) in both sexes. 32.3% of males and 10.3% of females had mild hyperhomocysteinemia (tHcy>15mumol/l). tHcy levels were significantly higher in smokers than in non-smokers (geometric mean +/- SD, 14.58 mumol/l +/- 1.44 Vs.12.71 mumol/l +/- 1.37, p<0.05) and in alcohol consumers than in non-consumers (geometric mean +/- SD, 14.53 mumol/l +/- 1.43 Vs.12.14 mumol/l +/- 1.32, p< 0.02). In males, tHcy levels were negatively related to serum insulin (r= -0.397, p<0.001) and BMI (r= -0.244, p <0.02) and positively related to serum creatinine (r=0.235, p<0.02). In females, there was a positive relationship between tHcy and systolic blood pressure (r= 0.239, p<0.02) but there was no significant correlation with serum insulin. In both sexes, serum tHcy levels strongly correlated with serum folate (r= -0.412, p<0.001). There were no significant associations between tHcy and serum lipids. Stepwise regression analysis confirmed the associations between tHcy and folate (p<0.001 in both sexes), insulin (p=0.026 in males) and creatinine (p=0.036 in males). CONCLUSION: Low intake of folate, alcohol consumption and smoking were associated with increased tHcy concentrations. Serum insulin and creatinine were independent correlates of tHcy in males, but not in females. Difference in tHcy levels between sexes may partly be attributed to differences in lean muscle mass and to a metabolic link between creatinine synthesis and homocysteine production. Insulin may regulate serum tHcy concentrations by homocysteine remethylation or by increasing homocysteine clearance.
Effect of mebendazole threapy in pregnancy on birth outcome
(Sri Lanka Medical Association, 1998) de Silva, N.; Sirisena, J.; Gunasekera, D.; de Silva, J.
OBJECTIVES : A prospective, unmatched, case-control study was done to assess the safety of mebendazole threapy in pregnancy, a hitherto uninvestigated factor. DESIGN : All women delivering in the University Obstetrics Unit of the Ragama Teaching Hospital between May 1996 and, March 1997 were administered a questionnaire soon after delivery. Details of the birth and the baby were recorded; suspected defects were confirmed by a paediatrician. The incidence of congenital defects in babies of mothers who had taken mebendazole during the pregnancy was compared with the incidence among those who had not taken an anthelmintic (controls). Data analysis was done using Epi Info 6.03. RESULTS : Of 3688 women, 73.5% had taken mebendazole, 24.8% had not taken any any anthelmintic , 1.1% had taken an anthelmintic but could not identify it and 0.6% had taken pyrantel or albedazole. The incidence of birth defects was 2.36% {64/2711) in the mebendazole group compared with 2.3% (21/913) in the controls (odds ratio 1.03, 95% confidence limits 0.61 - 1.75). This difference was not statistically significant even when corrected for other known risk factors by stratified analysis . Data regarding timing of mebendazole threapy was available for 2660 women; 6.9% in the first trimester, 83.8% in the second, and 9.2% in the third. The incidence of birth defects among women who had taken mebendazole in the first trimester was 3.24% (6/185). giving an odds ratio of 1.42 against the controls; this was also not statistically significant.CONCLUSIONS : The use of mebendazole in pregnancy does not lead to a significant increase in the risk of congenital defects.
Efficacy of a dengue vaccine candidate (TAK-003) in healthy children and adolescents two years after vaccination
(University of Chicago Press, 2022) López-Medina, E.; Biswal, S.; Saez-Llorens, X.; Borja-Tabora, C.; Bravo, L.; Sirivichayakul, C.; Vargas, L.M.; Alera, M.T.; Velásquez, H.; Reynales, H.; Rivera, L.; Watanaveeradej, V.; Rodriguez-Arenales, E.J.; Yu, D.; Espinoza, F.; Dietze, R.; Fernando, L.; Wickramasinghe, P.; Moreira Jr, E.D.; Fernando, A.D.; Gunasekera, D.; Luz, K.; da Cunha, R.V.; Tricou, V.; Rauscher, M.; Liu, M.; LeFevre, I.; Wallace, D.; Kosalaraksa, P.; Borkowski, A.; TIDES study group.
BACKGROUND: Takeda's dengue vaccine is under evaluation in an ongoing Phase 3 efficacy study; we present an update after 2 years. METHODS: 20,099 children (4-16 years old) were randomized to receive two doses of TAK-003 or placebo three months apart and are under long-term febrile surveillance to detect dengue by serotype-specific RT-PCR. (NCT02747927). RESULTS: Cumulative efficacy against dengue over ~27 months since first dose was 72.7% (95% CI: 67.1 - 77.3), which included efficacy of 67.0% (95% CI: 53.6 - 76.5) in dengue-naïve and 89.2% (82.4 - 93.3) against hospitalized dengue. In the second year after vaccination, a decline in efficacy was observed [56.2% (42.3 - 66.8)] with the largest decline in 4 - 5 year-old children [24.5% (-34.2 - 57.5)]; efficacy was 60.6% (43.8 - 72.4) in 6 - 11 year and 71.2% (41.0 - 85.9) in 12 - 16 year age groups. As TAK-003 efficacy varies by serotype, changes in serotype dominance partially contributed to the efficacy differences in year by year analysis. No related serious adverse events occurred during the second year. CONCLUSION: TAK-003 demonstrated continued benefit independent of baseline serostatus in reducing dengue with some decline in efficacy during the second year. Three-year data will be important to see if efficacy stabilizes or declines further. KEYWORDS: Dengue; TAK-003; efficacy; immunogenicity; persistence; safety; vaccine.
Efficacy of a tetravalent dengue vaccine in healthy children aged 4-16 years: A Randomised, placebo-controlled, phase 3 trial
(J. Onwhyn, 2020) Biswal, S.; Borja-Tabora, C.; Martinez Vargas, L.; Velásquez, H.; Theresa Alera, M.; Sierra, V.; Johana Rodriguez-Arenales, E.; Yu, D.; Wickramasinghe, V.P.; Duarte Moreira, E. Jr.; Fernando, A. D.; Gunasekera, D.; Kosalaraksa, P.; Espinoza, F.; López-Medina, E.; Bravo, L.; Tuboi, S.; Hutagalung, Y.; Garbes, P.; Escudero, I.; Rauscher, M.; Bizjajeva, S.; LeFevre, I.; Borkowski, A.; Saez-Llorens, X.; Wallace, D.; TIDES study group
BACKGROUND: A substantial unmet need remains for safe and effective vaccines against dengue virus disease, particularly for individuals who are dengue-naive and those younger than 9 years. We aimed to assess the efficacy, safety, and immunogenicity of a live attenuated tetravalent dengue vaccine (TAK-003) in healthy children aged 4-16 years. METHODS: We present data up to 18 months post-vaccination from an ongoing phase 3, randomised, double-blind trial of TAK-003 in endemic regions of Asia and Latin America (26 medical and research centres across Brazil, Colombia, Dominican Republic, Nicaragua, Panama, Philippines, Sri Lanka, and Thailand). Healthy children aged 4-16 years were randomly assigned 2:1 (stratified by age and region) to receive two doses of TAK-003 or two doses of placebo, 3 months apart. Investigators, participants and their parents or guardians, and sponsor representatives advising on trial conduct were masked to trial group assignments. Participants presenting with febrile illness were tested for virologically confirmed dengue (VCD) by serotype-specific RT-PCR. In timeframes beginning 30 days post-second dose, the primary endpoint (overall vaccine efficacy) was assessed in the first 11 months, and the secondary endpoints (efficacy by baseline serostatus, serotype, hospitalised dengue, and severe dengue) in the first 17 months. This study is registered with ClinicalTrials.gov, NCT02747927. FINDINGS: 20 099 participants were randomly assigned and vaccinated between Sept 7, 2016, and Aug 18, 2017; 19 021 (94·6%) were included in the per protocol analysis, and 20 071 (99·9%) in the safety set. The primary endpoint was achieved with an overall vaccine efficacy of 80·2% (95% CI 73·3 to 85·3; 61 cases of VCD in the TAK-003 group vs 149 cases of VCD in the placebo group). In the secondary endpoint assessment timeframe, an overall vaccine efficacy of 73·3% (95% CI 66·5 to 78·8) was observed. Analysis of secondary endpoints showed efficacies of 76·1% (95% CI 68·5 to 81·9) in individuals who were seropositive at baseline, 66·2% (49·1 to 77·5) in individuals who were seronegative at baseline, 90·4% (82·6 to 94·7) against hospitalised dengue, and 85·9% (31·9 to 97·1) against dengue haemorrhagic fever. Efficacy varied by individual serotypes (DENV 1, 69·8% [95% CI 54·8 to 79·9]; DENV 2, 95·1% [89·9 to 97·6]; DENV 3, 48·9% [27·2 to 64·1]; DENV 4, 51·0% [-69·4 to 85·8]). Cumulative rates of serious adverse events were similar in TAK-003 (4·0%) and placebo (4·8%) recipients, and were consistent with expected medical disorders in the study population. Infection was the most frequent reason leading to serious adverse events. 20 participants (<0·1% of the safety set) were withdrawn from the trial due to 21 adverse events by the end of part two; 14 of these participants received TAK-003 and six received placebo. INTERPRITATION: TAK-003 was well tolerated and efficacious against symptomatic dengue in children regardless of serostatus before immunisation. Vaccine efficacy varied by serotype, warranting continued follow-up to assess longer-term vaccine performance. FUNDING: Takeda Vaccines.
Exposure to environmentally relevant concentrations of acetaminophen increases the vitellogenin expression in juvenile Danio rerio (zebrafish)
(Faculty of Science, University of Kelaniya Sri Lanka, 2024) Ishara, A. A. A. P.; Perera, K. D. C.; Gunathilaka, N.; Gunasekera, D.; Wickramasinghe, P. M. T. B.; Rajapaksa, G.
Non-Steroidal Anti Inflammatory Drug acetaminophen has become the most common pharmaceutical pollutant in aquatic ecosystems. Recently a non-classical pathway of endocrine disruption is suggested with acetaminophen. Early life stages account for a significant level of hormone-regulated development therefore, it is important to assess whether early life exposure to acetaminophen could result in endocrine disruption in aquatic organisms. Vitellogenin (Vtg) is an egg precursor protein produced in response to estrogen and serves as a reliable molecular marker to assess the xenoestrogen-induced endocrine disruption. Therefore, this study was carried out to investigate the effects of long-term juvenile exposure to environmentally relevant concentrations of acetaminophen on vitellogenin expression in model organism, zebrafish (Danio rerio). Zebrafish of 25 days post fertilization were maintained under environmentally relevant acetaminophen concentrations of 10 μg/L, and 75 μg/L, and in control tanks for 60 days in triplicate with 18 fish in each tank. Vtg-1, the most predominant type of Vtg mRNA produced in zebrafish liver was analyzed using qRT-PCR with β-actin as the housekeeping gene. Furthermore, hepatic vitellogenin expression has been observed with hematoxylin and eosin staining of zebrafish hepatic sections. According to the results, acetaminophen-exposed zebrafish showed higher Vtg-1 gene expression than the fish of control treatment. 10 μg/L acetaminophen showed the highest Vtg-1 expression followed by 75 μg/L of acetaminophen in fish. Hematoxylin and eosin staining of the liver of male zebrafish from control treatments appeared eosinophilic indicating the absence of Vtg while hepatocytes of control female fish were more basophilic indicating Vtg expression. However, under 10 μg/L of acetaminophen exposure, male and female fish hepatocytes appeared more basophilic than the control treatment indicating acetaminophen-induced Vtg secretion. However, 10 μg/L concentration shows a higher basophilic nature compared to 75 μg/L, especially in female fish. The lowered Vtg expression in 75 μg/L can be due to the increased hepatotoxicity caused by the higher doses of acetaminophen which overrides the physiological activity in acetaminophentreated fish, dilated capillaries were observed compared to fish in the control treatment. It has been demonstrated that estrogenic xenobiotics stimulate the synthesis of Vtg by acting on the liver's estrogen receptors. Increased Vtg -1 mRNA in low acetaminophen concentration as shown in qRT- PCR and liver histopathology postulate an “estrogen-like activity of acetaminophen”. The results indicate that acetaminophen has the potential to increase vitellogenin expression in zebrafish even under environmentally relevant low concentrations indicating an endocrine disruption effect during juvenile exposure.
Long-term efficacy and safety of a tetravalent dengue vaccine (TAK-003): 4·5-year results from a phase 3, randomised, double-blind, placebo-controlled trial
(Elsevier, 2024) Tricou, V.; Yu, D.; Reynales, H.; Biswal, S.; Saez-Llorens, X.; Sirivichayakul, C.; Lopez, P.; Borja-Tabora, C.; Bravo, L.; Kosalaraksa, P.; Vargas, L.M.; Alera, M.T.; Rivera, L.; Watanaveeradej, V.; Dietze, R.; Fernando, L.; Wickramasinghe, V.P.; Moreira, E.D.; Fernando, A.D.; Gunasekera, D.; Luz, K.; Oliveira, A.L.; Tuboi, S.; Escudero, I.; Hutagalung, Y.; Lloyd, E.; Rauscher, M.; Zent, O.; Folschweiller, N.; LeFevre, I.; Espinoza, F.; Wallace, D.
BACKGROUND: About half of the world's population lives in dengue-endemic areas. We aimed to evaluate the long-term efficacy and safety of two doses of the tetravalent dengue vaccine TAK-003 in preventing symptomatic dengue disease of any severity and due to any dengue virus (DENV) serotypes in children and adolescents. METHODS: In this ongoing double-blind, randomised, placebo-controlled trial, we enrolled healthy participants aged 4-16 years at 26 medical and research centres across eight dengue-endemic countries (Brazil, Colombia, Dominican Republic, Nicaragua, Panama, Philippines, Sri Lanka, and Thailand). The main exclusion criteria were febrile illness (body temperature ≥38°C) at the time of randomisation, hypersensitivity or allergy to any of the vaccine components, pregnancy or breastfeeding, serious chronic or progressive disease, impaired or altered immune function, and previous receipt of a dengue vaccine. Participants were randomly assigned 2:1 (stratified by age and region) using an interactive web response system and dynamic block assignment to receive two subcutaneous doses of TAK-003 or placebo 3 months apart. Investigators, participants, and their parents or legal guardians were blinded to group assignments. Active febrile illness surveillance and RT-PCR testing of febrile illness episodes were performed for identification of virologically confirmed dengue. Efficacy outcomes were assessed in the safety analysis set (all randomly assigned participants who received ≥1 dose) and the per protocol set (all participants who had no major protocol violations), and included cumulative vaccine efficacy from first vaccination to approximately 4·5 years after the second vaccination. Serious adverse events were monitored throughout. This study is registered with ClinicalTrials.gov, NCT02747927. FINDINGS: Between Sept 7, 2016, and March 31, 2017, 20 099 participants were randomly assigned (TAK-003, n=13 401; placebo, n=6698). 20 071 participants (10 142 [50·5%] males; 9929 [49·5%] females; safety set) received TAK-003 or placebo, with 18 257 (91·0%) completing approximately 4·5 years of follow-up after the second vaccination (TAK-003, 12 177/13 380; placebo, 6080/6687). Overall, 1007 (placebo: 560; TAK-003: 447) of 27 684 febrile illnesses reported were virologically confirmed dengue, with 188 cases (placebo: 142; TAK-003: 46) requiring hospitalisation. Cumulative vaccine efficacy was 61·2% (95% CI 56·0-65·8) against virologically confirmed dengue and 84·1% (77·8-88·6) against hospitalised virologically confirmed dengue; corresponding efficacies were 53·5% (41·6-62·9) and 79·3% (63·5-88·2) in baseline seronegative participants (safety set). In an exploratory analysis, vaccine efficacy was shown against all four serotypes in baseline seropositive participants. In baseline seronegative participants, vaccine efficacy was shown against DENV-1 and DENV-2 but was not observed against DENV-3 and low incidence precluded evaluation against DENV-4. During part 3 of the trial (approximately 22-57 months after the first vaccination), serious adverse events were reported for 664 (5·0%) of 13 380 TAK-003 recipients and 396 (5·9%) of 6687 placebo recipients; 17 deaths (6 in the placebo group and 11 in the TAK-003 group) were reported, none were considered study-vaccine related. INTERPRETATION: TAK-003 demonstrated long-term efficacy and safety against all four DENV serotypes in previously exposed individuals and against DENV-1 and DENV-2 in dengue-naive individuals. FUNDING: Takeda Vaccines. TRANSLATIONS: For the Portuguese, Spanish translations and plain language summary of the abstract see Supplementary Materials section.
Prevalence of metabolic syndrome in a Sri Lankan community
(Sri Lanka Medical Association, 2008) Chackrewarthy, S.; Gunasekera, D.; de Silva, L.D.R.; Pathmeswaran, A.; Wijekoon, C.N.; Ranawaka, U.K.; Mizoue, T.; Kato, N.
OBJECTIVE: To estimate the prevalence of metabolic syndrome (MetS) in a Sri Lankan community. Limited information is available about MetS in Sri Lankans. DESIGN, SETTING AND METHODS: A total of 2948 individuals (1345 males and 1603 females) who participated in the Ragama Health Study comprised the study population. Prevalence of MetS was estimated using three widely used criteria: International Diabetes Federation (IDF), WHO and National Cholesterol Education Programme - Adult Treatment Panel III (NCEP-ATP III). RESULTS: Age and sex adjusted prevalence rates of MetS were 38.9%, 38.9% and 41.6% as defined by IDF, WHO and NCEP-ATP III respectively. Prevalence increased with age (for age groups 35-44, 45-54 and 55- 65 years respectively; IDF - 27.9%, 40,1%, 42.9% ; WHO - 28.7%, 43.2%, 52.6%; NCEP ATP III - 34.6%, 46.7%, 50.6%; P<0.001 in all). MetS was commoner in women (IDF - 45.8% Vs. 23.0%, P<0.001; WHO - 37.3% Vs. 40.5%, P>0.05; NCEP-ATP III - 49.8% Vs. 33.1%, P<0.001). Prevalence of central obesity (using Asian cutoff values) was higher in women. (70.8% Vs. 35.5%, P<0.001). CONCLUSION: Prevalence of MetS is high in this community. Preventive measures towards reducing trie risks associated with MetS should be promoted.
A secondary metabolite with in vitro radical scavenging activity from endolichenic fungus Daldinia eschscholzii found in lichen, Parmotrema sp. in Sri Lanka
(Journal of the National Science Foundation of Sri Lanka, 2020) Manthrirathna, M.; Kandiah, R.; Gunasekera, D.; Samanthi, K.; Welideniya, D.; Maduranga, H.; Paranagama, P.
Endolichenic fungi, an unexplored group of microorganisms, are a promising source of bioactive compounds. Secondary metabolites were isolated from the chloroform fraction of crude ethyl acetate extract of endolichenic fungus Daldinia eschscholzii inhabiting the lichen, Parmotrema sp. in Sri Lanka. Two pure compounds, 1 and 2 were isolated and the structures were identified using 1H-, 13C-, 2D- nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) data. Compound 1 did not show any radical scavenging activity in DPPH assay. Compound 2, identified as 8-methoxynaphthalen-1-ol showed strong radical scavenging ability in the DPPH assay with a half maximal inhibitory concentration (IC50) of 10.2 ± 5.8 µg/ mL. The activity of compound 2 was higher than that of the standard, butylated hydroxy toluene (BHT).
Three years efficacy and safety of Takeda's dengue vaccine candidate (TAK-003)
(Oxford University Press, 2022) Rivera, L.; Biswal, S.; Sáez-Llorens, X.; Reynales, H.; López-Medina, E.; Borja-Tabora, C.; Bravo, L.; Sirivichayakul, C.; Kosalaraksa, P.; Vargas, L.M.; Yu, D.; Watanaveeradej, V.; Espinoza, F.; Dietze, R.; Fernando, L.; Wickramasinghe, P.; Duarte Moreira, E. J.; Fernando, A. D.; Gunasekera, D.; Luz, K.; Venâncio da Cunha, R.; Rauscher, M.; Zent, O.; Liu, M.; Hoffman, E.; LeFevre, I.; Tricou, V.; Wallace, D.; Alera, M.T.; Borkowski, A.
Background: Takeda's live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across eight dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year post-vaccination. This exploratory analysis provides an update with cumulative and third year data. Methods: Healthy 4-16 year-olds (n=20,099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific RT-PCR. Results: Cumulative efficacy after three years was 62.0% (95% confidence interval: 56.6%, 66.7%) against virologically-confirmed dengue (VCD) and 83.6% (76.8%, 88.4%) against hospitalized VCD. Efficacy was 54.3% (41.9%, 64.1%) against VCD and 77.1% (58.6%, 87.3%) against hospitalized VCD in baseline seronegatives, and 65.0% (58.9%, 70.1%) against VCD and 86.0% (78.4%, 91.0%) against hospitalized VCD in seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5%, 54.7%), while efficacy against hospitalized VCD was sustained at 70.8% (49.6%, 83.0%). Rates of serious adverse events were 2.9% in TAK-003 group and 3.5% in placebo group during the ongoing long-term follow-up (i.e. second half of the three years following vaccination), but none were related. No important safety risks were identified. Conclusions: TAK-003 was efficacious against symptomatic dengue over three years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned.