Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Detection of pathogenic Leptospira with rapid extraction followed by recombinase polymerase amplification (RPA) and quantitative polymerase chain reaction (qPCR) assay-A comprehensive study from Sri Lanka(Public Library of Science, 2024) Uduwawala, H.; Manamperi, A.; Gunaratna, G.P.S.; Karunanayake, L.; Ceruti, A.; Wahed, A.A.E.; Fernando, L.; Premaratna, R.; Hapugoda, M.Leptospirosis is the most widespread zoonosis in the world. The disease is more prevalent in tropical regions where the majority of developing countries are located. Leptospirosis is considered a protean manifestation zoonosis with severity of the disease ranging from a mild febrile illness to a severe and life-threatening illness. Clinical symptoms of leptospirosis overlap with other tropical febrile illnesses. Early, rapid, and definitive diagnosis is important for effective patient management. Since Polymerase Chain Reaction (PCR)-based assays are not readily available in most clinical settings, there is a need for an affordable, simple, and rapid diagnostic test. Quantitative PCR (qPCR) and Recombinase Polymerase Amplification (RPA) were implemented at the Faculty of Medicine, University of Kelaniya, and a prospective study to evaluate RPA for diagnosis of acute phase of leptospirosis was conducted. Results indicate that RPA and qPCR were positive in 81% (98/121) of the total positive and acute clinical samples. Of the 81 positive MAT confirmed patients 60 (74%) and 53 (65%) were positive with qPCR and RPA respectively. Retrospective evaluation revealed a high diagnostic accuracy (sensitivity-70% and specificity-87%) of RPA compared to MAT as the reference gold standard. Results further suggest that there is no significant difference between the two assays, qPCR and RPA-SwiftX (P = 0.40). Laboratory procedures for the extraction and detection by qPCR in the laboratory have been optimized to obtain results within 6 hours. However, the RPA-SwiftX method under field conditions took 35 minutes. The RPA-SwiftX method could replace the qPCR which shows similar sensitivity and specificity. Therefore, RPA established under the current study presents a powerful tool for the early and rapid diagnosis of leptospirosis at point-of-care.Item 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.Item Epidemiological evidence of acute transmission of zika virus infection in dengue suspected patients in Sri-Lanka(Elsevier, 2023) Ngwe, T.M.M.; Raini, S.K.; Fernando, L.; Gunawardene, Y.I.N.S.; Inoue, S.; Takamatsu, Y.; Urano, T.; Muthugala, R.; Hapugoda, M.; Morita, K.Background: Zika Virus (ZIKV) is a re-emerging, arthropod-borne flavivirus transmitted by Aedes mosquitoes (Ae. aegypti and Ae. albopictus). The coexistence of dengue virus (DENV) and ZIKV concurrently has been associated with a wide array of neurological complications, which may influence the clinical outcomes of infections. Sri Lanka witnessed a severe dengue epidemic in 2017, characterized by extraordinary and severe disease manifestations with considerable morbidity. Therefore, this study assessed the potential occurrence of ZIKV infection during DENV outbreak in Sri Lanka from 2017 to 2019, which could bear substantial implications for public health. Methods: Five hundred ninety-five serum samples were procured from individuals suspected of dengue and admitted to Kandy National Hospital between 2017 and 2018 and the Negombo District General Hospital between 2018 and 2019. These samples underwent quantitative real-time RT-PCR (qRT-PCR) to identify the presence of the ZIKV gene, while enzyme-linked immunosorbent assay was employed to detect ZIKV-specific IgM and IgG antibodies. Focus reduction neutralization tests were subsequently conducted to confirm ZIKV infection. Results: Among the 595 serum samples, 6 (1.0%) tested positive for ZIKV using qRT-PCR. Anti-ZIKV IgM and IgG were identified in 18.0% and 38.6% patients. Sixty-six (11.0%) samples demonstrated the presence of anti-ZIKV IgM and IgG. Within ZIKV IgM-positive samples, 2.2% exhibited neutralizing antibodies against ZIKV. Through the implementation of qRT-PCR, ZIKV IgM detection, and neutralization testing, 2% and 3.7% cases of ZIKV infections were confirmed in the Kandy and Negombo regions, respectively. Conclusion: This study is the inaugural endeavor to substantiate the existence of ZIKV infection in Sri Lanka utilizing molecular and serological analysis. The findings of this investigation imply that ZIKV was circulating throughout the 2017-2019 DENV outbreak. These results underscore the necessity for improved preparedness for future outbreaks, fortifying governmental policies on public health, and establishing effective early warning systems regarding the emergence of these virusesItem Knowledge, challenges, quality of life and their associated factors among adult patients with Type 1 diabetes attending National Diabetes Centre - Rajagiriya(Faculty of Medicine, University of Kelaniya, Sri Lanka, 2021) Fernando, L.Introduction: Literature on type 1 diabetes mellitus (T1DM) and its effects on daily living, financial, educational, psychosocial challenges and quality of life is scare in Sri Lanka. Objectives: To describe the knowledge, challenges, quality of life and their associated factors among adult patients with T1 DM attending National Diabetes Centre, Rajagiriya. Method: A descriptive cross-sectional study was conducted among 228 patients with T1DM, on treatment for at least one year duration attending National Diabetic Centre, Rajagiriya. Self-administered questionnaires were circulated as google forms. Descriptive statistics was performed and analysed. P<0.05 was taken as the significance level. Results: Majority (70%) were between 18-27 years of age with mean age 25.54 years (SD=5.690). Age of disease onset was less than 15 years among 82% of patients. Mean Knowledge scores on insulin therapy, emergency management and chronic complications were 67.76 (SD=0.49), 42.92 (SD=0.5) and 81.49 (SD=0.5) respectively. Overall knowledge, knowledge on insulin therapy and acute complications were statistically significant among those better educated (p<0.05). Majority (54.87%) had good quality of life. Majority encountered family issues (30.3%). Better quality of life was significantly associated with higher monthly income (p<0.05) Conclusions: Majority had satisfactory knowledge on insulin therapy and chronic complications but poor knowledge on acute complications. Those educated above O/L had better knowledge on insulin therapy and acute complications. Majority had good quality of life and those with higher income had a better quality of life.Item 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.Item Pre-defined competency level based instructional design model for learning Anatomy in an undergraduate medical curriculum(South East Asia Regional Association for Medical Education (SEARAME), 2021) Abeykoon, I.; Fernando, L.; Fernando, A.; Weerasooriya, T.; Chandratilake, M.ABSTRACT: The paper presents a competency based instructional design model to teach gross Anatomy in an undergraduate medical course. The main objectives of the presented instructional design model is to allow space for identification of finer demarcations for expected competencies while allowing the students to possess a broader understanding of the discussed areas under each competency level. Here the traditional semester will be split into three competency levels and within each competency level the entire region expected to be discussed will be presented. However, the first competency level will discuss the given area superficially with details being introduced during second and third competency levels. The center of focus as well as teaching learning modalities will also evolve with increasing competency levels making the presented instructional design model a more dynamic than a static approach. KEYWORDS: Medical education, Anatomy, Competency based education, Higher education, Educational modelItem 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.Item Predictive value of persistent NS1 antigen positivity beyond 3rd day for dengue haemorrhagic fever in Sri Lankan children.(London : Biomed Central, 2019) Manamperi, M.; Jayamanne, B. D. W.; Somaratne, T.; Perera, N.; Fernando, L.OBJECTIVE:Dengue haemorrhagic fever (DHF) is a major public health concern responsible for significant morbidity in both adult and paediatric populations in Sri Lanka. This study examined if persistent non structural protein 1 (NS1) antigen positivity beyond day 3 was predictive of the occurrence of dengue haemorrhagic fever. The patients were followed up during their in-hospital stay and the severity of the illness was classified according to the WHO classification. The NS1 antigen test was repeated after day 3 of the onset of illness, at least 2 days after the initial test. RESULTS: One hundred and fifty-seven patients were enrolled. Persistent NS1 antigen test positivity after day 3 of the illness was not predictive of subsequent development of DHF. Out of multiple other demographic and illness related factors assessed, only having a secondary dengue infection was associated with a high risk of DHF (relative risk = 3.077, 95% CI 1.361, 6.954). Persistent NS1 positivity on day 3 may not be indicative of disease severity. However results need to be confirmed by a larger study with quantitative NS1 testing.Item Chiari malformation type 1 presenting as unilateral progressive foot drop: a case report and review of literature(BioMed Central, 2018) Jayamanne, C.; Fernando, L.; Mettananda, S.BACKGROUND: Foot drop is a disabling clinical condition with multiplicity of causes, which requires detailed evaluation to identify the exact aetiology. Here, we report an extremely rare cause of foot drop in a child, which if not recognized early, could lead to multiple complications. CASE PRESENTATION: A 6-year-old girl presented with difficulty in walking and left sided foot droop for1-month duration. On examination she had reduced muscle power in dorsiflexors and plantar flexors and diminished knee and absent ankle jerk in the left side. Sensory loss was noted in L4 and L5 dermatomes on the left side. Superficial abdominal reflex was absent on the left side while preserved in the right. Nerve conduction and electromyography revealed nerve root or spinal cord cause for the foot drop. These results prompted ordering MRI spine and brain which revealed Chiari malformation type-1 with holocord syrinx extending from the cervicomedullary junction to conus medullaris. CONCLUSIONS: This case highlights the importance of considering broad differential diagnosis for foot drop and value of the complete neurological examination including superficial reflexes in arriving at a diagnosis. Prompt diagnosis helped to early neurosurgical referral and intervention which is an important prognostic factor.Item A comparative study of subjective experiences related to driving among outpatient psychotropic users and controls in Ragama, Sri Lanka(Sri Lanka College of Psychiatrists, 2016) Chandradasa, M.; Champika, L.; Amarasuriya, M.; Wijelakshman, P.; Bandara, S.; Ranaweera, T.; Fernando, L.Aim: To identify and explore the impact of illness and medications on the driving of patients visiting an outpatient clinic. Method: A retrospective-cohort design was used. The data was collected using a semi-structured, intervieweradministered questionnaire among consecutive patients with schizophrenia or bipolar disorder. An age, gender and vehicle matched control group was obtained. Result: A total of 2887 consecutive clinic patients were asked about driving and 57 (1.9%) who had driven a vehicle regularly during the last 12 months were included in the study group. A majority were in the 30-45 year category (47%). All were men and a majority were motor-bike riders (53%). Collision-accidents were experienced by 42% of participants during the last 12 months. Conclusion: The patient group had lower hours of driving per week, less subjectively claimed earning per day and more with at least one collision-accident during the past year compared to the control group.