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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Forecasting dengue incidence based on entomological indices, population density, and meteorological and environmental variables in the Gampaha District of Sri Lanka(Elsevier Ltd, 2024) Dalpadado, R.; Amarasinghe, D.; Gunathilaka, N.; Wijayanayake, A.N.No abstract availableItem Development of a complex intervention package for dengue prevention(Ministry of Health, Sri Lanka, 2022) Rajapaksha, R.M.N.U.; Abeysena, C.; Balasuriya, A.; PannilaHetti, N.; Alagiyawanna, A.; Manilgama, S.INTRODUCTION: Complex interventions are widely used in public health practices with noteworthy health impacts. Communication for Behavioural Impact (COMBI) plan is an effective method directed at enacting behaviour change to benefit health and social development which encourage precise behavioural outcomes and is effective in planning a behavioural change for dengue control. The aim of this study was to develop an intervention package to change the behaviour to prevent dengue in one of the highest dengue-endemic areas of Sri Lanka. METHODS: The development of the intervention package was formulated according to the two phases, the ‘Theoretical phase’ and ‘Modelling phase’ of the framework for ‘Developing and Evaluating Complex Interventions’. World Health Organization’s 10 key steps in planning COMBI strategies were followed in order to develop the present intervention package. A situational market analysis was conducted in the highest dengue-endemic area in Kurunegala district to identify the Specific Behavioural Objectives (SBOO) for the COMBI plan. The development of the COMBI plan was conducted using the mixed methodological approach including quantitative and qualitative designs. RESULTS: The overall goal of the COMBI plan was to decrease the morbidity and mortality due to dengue illness by improving the dengue prevention behaviours among householders. The SBOO for the plan were to improve the proper waste management practices according to the ‘3R concept’ (Reduce, Reuse and Re-cycling) and to improve the dengue prevention practices by 30 minutes of weekly cleaning. The strategies of intervention package were to conduct a community empowerment program to improve household waste management and weekly practices on dengue prevention by conducting administrative mobilization and public relationship, public advocacy, community mobilization, personal selling, advertising, and point of service promotion during follow-up. CONCLUSION: Developing a COMBI plan for an area after the identification of SBOO would be feasible to implement in order to empower the community to prevent dengue and improve community health services.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 Health seeking behaviours, dengue prevention behaviours and community capacity for sustainable dengue prevention in a highly dengue endemic area, Sri Lanka(BioMed Central, 2023) Rajapaksha, R.M.N.U.; Abeysena, C.; Balasuriya, A.INTRODUCTION: Dengue has become a major health problem in globally as well as locally. The delay in health-seeking is significantly associated with complications leading to severe dengue and active engagement of communities needs to minimize the delays in management to control epidemics. The aim of the study was to evaluate the relationship between sociodemographic characteristics and householders' Health-Seeking Behaviours (HSB), Dengue-Prevention Behaviours (DPB), and Community Capacities (CC) for sustained dengue prevention in Sri Lanka, a country with a high dengue endemicity. METHODS: A cross-sectional analytical study was carried out in a district with the highest dengue endemicity from January to April 2019. Of the householders, 532 were chosen randomly. A pre-tested, validated, and interviewer-administered questionnaire was used to assess HSB and DPB. The HSB was assessed using three aspects, initial response for fever management, the duration of blood testing and initial response if suspected dengue. The DPB assessment was evaluated using 'waste, outdoor water container, indoor water container, roof gutter and water storage management'. 'Dengue Community Capacity Assessment Tool', with 14 key items was used to assess the level of community capacity for dengue prevention. Out of the total, ≥ 50% was considered as an "adequate" HSB, DPB and CC. Multiple logistic regression was performed to control confounding effects. The results were expressed as adjusted Odds-Ratios (aOR) and 95% Confidence Intervals (CI). RESULTS: The response rate was 93.2% (n = 496). Among them, 44.6% (n = 221) had adequate overall HSB, and 19.2% (n = 95) had adequate DPB. Householders who have ≤ 4 family members are 1.74 times (aOR = 1.74; 95% CI: 1.17 - 2.61) more likely to have adequate HSB and 1.85 times (aOR = 1.85; 95% CI: 1.11 - 3.09) more likely to have adequate DPB. The age group of 46 to 70 years' individuals (aOR = 1.74; 95% CI:1.12 - 2.92), and who engaged in employment (aOR = 1.68; 95% CI: 1.05 - 2.67) were more likely to have adequate DPB than the group of 18 to 45 years and the non-employed individuals respectively. Of them, 24.6% (n = 122) perceived that they have adequate CC. The householders who have per-capita income < USD 50 are 1.95 times (aOR = 1.95; 95%CI:1.11 - 3.40) more likely to have adequate CC. CONCLUSION: The HSB, DPB and CC need to be improved to change the behaviour for sustainable dengue prevention and community capacity-building programmes need to be conducted in the Kurunegala district, Sri Lanka.Item A cluster-randomized, placebo-controlled trial to evaluate the efficacy of a spatial repellent (Mosquito Shield™) against Aedes-borne virus infection among children ≥ 4-16 years of age in the Gampaha District, Sri Lanka: study protocol (the AEGIS program)(BioMed Central, 2023) Tissera, H.; Dheerasinghe, D.S.A.F.; Malavige, N.; de Silva, H.A.; Morrison, A.C.; Scott, T.W.; Reiner, R.C. Jr.; Grieco, J.P.; Achee, N.L.BACKGROUND: Spatial repellents (SRs) have been widely used for prevention of mosquito bites, but their efficacy in reducing Aedes-borne viruses (ABV) has not been tested rigorously at large scale in Asia. To address this knowledge gap, a trial to evaluate the efficacy of Mosquito Shield™, a transfluthrin SR, was developed in Gampaha District of Sri Lanka across three Medical Officer of Health areas; i.e., Negombo, Wattala, and Kelaniya. METHODS: This trial is a cluster-randomized, placebo-controlled, double-blinded clinical trial. A total of ~14,430 subjects aged ≥ 6 months in 30 clusters (15 intervention, 15 placebo) from ~3900 households (HH) will be randomly selected for enrolment into a "febrile surveillance cohort." A subset of the surveillance cohort, ~3570 subjects aged ≥4-16 years that test seronegative (naïve) or are serologically positive for a previous single dengue virus (DENV) infection (monotypic) at baseline sampling, will be enrolled into a "longitudinal cohort" for measuring DENV infection based on laboratory-confirmed seroconversion during the trial. Persons identified positive for antibodies against multiple DENV serotypes (multitypic) at baseline will be monitored for secondary analyses. Active ABV disease will be assessed using an enhanced passive surveillance system with case ascertainment performed in designated healthcare facilities. Serum samples will be taken from longitudinal cohort subjects within 1-2 weeks of when intervention is first deployed (T0) with additional samples taken ~12 (T1) and ~24 months (T2) from baseline sampling. DENV seroconversion and ABV active disease rates from baseline (pre-intervention) and follow-up (post-intervention) samples will be compared between intervention and placebo clusters. Participating houses will be monitored entomologically (indoor adult Aedes aegypti population densities and adult female blood fed status) within 3 months before intervention deployment and monthly during the intervention phase. Entomological surveys will monitor indoor adult Ae. aegypti population densities and blood fed status. Dengue incidence in each cohort will be estimated and compared to determine the public health benefit of using an SR. Entomological parameters will be measured to determine if there are entomological correlates of SR efficacy that may be useful for the evaluation of new SR products. DISCUSSION: The trial will serve as an efficacy assessment of SR products in South Asia. Results will be submitted to the World Health Organization Vector Control Advisory Group for assessment of public health value towards an endorsement to recommend inclusion of SRs in ABV control programs.Item Acute appendicitis during the recovery phase of dengue hemorrhagic fever: two case reports(BioMed Central, 2022) Thadchanamoorthy, V.; Ganeshrajah, A.; Dayasiri, K.; Jayasekara, N.P.Background: Dengue fever is one of the most common tropical diseases, with high prevalence in many tropical countries including Sri Lanka. Dengue infection can present from subclinical infection to dengue shock syndrome. Further, the disease also shows a variety of atypical presentations and has been reported to mimic a number of causes of acute abdomen. Case presentation: The authors report two children (a 6-year-old Tamil girl and an 8-year-old Muslim girl) who were diagnosed to have acute appendicitis during the early recovery phase of dengue hemorrhagic fever (DHF) and late recovery period of dengue hemorrhagic fever with platelet count of 92 × 103/cumm and 102 × 103/cumm, respectively. Both children were investigated with abdomen ultrasound as they developed severe abdominal pain and tenderness on palpation during the recovery phase, which was felt to be very unusual. Acute appendicitis was diagnosed in one child, while the other child had a ruptured appendicular abscess. Both children were treated with laparoscopic appendectomy and a 7-day course of intravenous antibiotics. Both children were reviewed in 1 month following treatment and had complete recovery. Conclusion: Although precise pathophysiology and associations of the surgical abdomen with dengue fever remain to be elucidated, there are known factors in dengue fever that can potentially lead to secondary bacterial infections and surgical abdomen. Awareness and increased suspicion by the clinician are paramount to detect such complications early, especially in children who demonstrate unusual clinical features during various stages of dengue infection.Item Bionomic aspects of dengue vectors Aedes aegypti and Aedes albopictus at domestic settings in urban, suburban and rural areas in Gampaha District, Western Province of Sri Lanka(BioMed Central, London, 2022) Dalpadado, R.; Amarasinghe, D.; Gunathilaka, N.; Ariyarathna, N.Background: The lack of information on behavioural patterns of Aedes aegypti and Aedes albopictus has become a significant limitation in vector control and disease management programmes. Therefore, the current study was focused on determining some bionomics aspects: breeding, resting, host-seeking and feeding preferences of Ae. aegypti and Ae. albopictus in Sri Lanka. Methods: Larval and adult surveys were conducted from April 2017 to April 2019 monthly in six selected Medical Officer of Health (MOH) areas in Gampaha Distinct, Western province, Sri Lanka, representing urban, suburban and rural settings. Resting preferences of adult mosquitoes were observed from indoor and outdoor places using a Prockopack aspirator. The information on resting height, surface, material and locality was recorded. Human-baited double-net traps were used to determine the host-seeking time of Aedes mosquitoes. Statistical differences in the spatial distribution of mosquitoes in selected MOH areas and prevalence of vectors were analysed using general linear model (GLM). A chi-square test was used to analyse the resting behaviour. Results: Total of 19,835 potential breeding sites were examined at 13,563 premises, and 18.5% (n = 1856) were positive for Aedes larvae. Distribution of Ae. aegypti and Ae. albopictus was statistically significant at species level (df = 1; F = 137.134; P < 0.05 GLM) and study setting (df = 2; F = 8.125; P < 0.05). Aedes aegypti breeding was found mainly in temporary removals (18.8%; n = 34), discarded non-degradables (12.15%; n = 22) and tyres (9.95%; n = 18). Natural (14.7%; n = 246) and temporary removals (13.6%; n = 227) and discarded non-reusable items were the key ovipositing sites for Ae. albopictus. In the adult mosquito survey, the majority was comprised of Ae. albopictus (54.5%; n = 999), which denoted exophilic nature (90.8%; n = 758), and 45.5% (n = 835) represented by Ae. aegypti mosquitoes who were mainly endophilic (84.3%; n = 842). Aedes aegypti rested on cloth hangings and curtains, followed by the furniture, while Aedes albopictus was predominant in outdoor vegetation. In both vectors, biting patterns denoted a typical diurnal pattern with two peaks of host-seeking and biting activity in the morning and afternoon. Conclusions: The majority (80%) of the larval habitats were artificial containers. The use of larvicides for vector control as the prominent measure is questionable since applying these chemicals may target only 20% of the total breeding grounds, which are permanent. The resting places of adult mosquitoes are mainly indoors. Therefore, using thermal space spraying of insecticide may not be appropriate, and indoor residual spraying is recommended as a suitable intervention to target adult mosquitoes. This study warrants a holistic vector control approach for all medically important mosquitoes and insects, ensuring the rational use of finance and resources.Item Development of the sterile Insect technique to control the dengue vector Aedes aegypti (Linnaeus) in Sri Lanka(Public Library of Science,San Francisco, 2022) Ranathunge, T.; Harishchandra, J.; Maiga, H.; Bouyer, J.; Gunawardene, Y.I.N.S.; Hapugoda, M.Background: The Sterile Insect Technique (SIT) is presently being tested to control dengue in several countries. SIT aims to cause the decline of the target insect population through the release of a sufficient number of sterilized male insects. This induces sterility in the female population, as females that mate with sterilized males produce no offspring. Male insects are sterilized through the use of ionizing irradiation. This study aimed to evaluate variable parameters that may affect irradiation in mosquito pupae. Methods: An Ae. aegypti colony was maintained under standard laboratory conditions. Male and female Ae. aegypti pupae were separated using a Fay and Morlan glass sorter and exposed to different doses of gamma radiation (40, 50, 60, 70 and 80 Gy) using a Co60 source. The effects of radiation on survival, flight ability and the reproductive capacity of Ae. aegypti were evaluated under laboratory conditions. In addition, mating competitiveness was evaluated for irradiated male Ae. aegypti mosquitoes to be used for future SIT programmes in Sri Lanka. Results: Survival of irradiated pupae was reduced by irradiation in a dose-dependent manner but it was invariably greater than 90% in control, 40, 50, 60, 70 Gy in both male and female Ae. aegypti. Irradiation didn't show any significant adverse effects on flight ability of male and female mosquitoes, which consistently exceeded 90%. A similar number of eggs per female was observed between the non-irradiated groups and the irradiated groups for both irradiated males and females. Egg hatch rates were significantly lower when an irradiation dose above 50 Gy was used as compared to 40 Gy in both males and females. Irradiation at higher doses significantly reduced male and female survival when compared to the non-irradiated Ae. aegypti mosquitoes. Competitiveness index (C) scores of sterile and non-sterile males compared with non-irradiated male mosquitoes under laboratory and semi-field conditions were 0.56 and 0.51 respectively at 50 Gy. Signification: Based on the results obtained from the current study, a 50 Gy dose was selected as the optimal radiation dose for the production of sterile Ae. aegypti males for future SIT-based dengue control programmes aiming at the suppression of Ae. aegypti populations in Sri Lanka.Item Expanded dengue syndrome presenting with acute liver failure, acute kidney injury, pancreatic involvement, coagulopathy, and multiple intracranial hemorrhages in a young child: a case report(BioMed Central, 2022) Thadchanamoorthy, V.; Dayasiri, K.Background: Dengue is a mosquito-borne viral infection that typically occurs in tropical and subtropical countries. The clinical manifestations of dengue infection range from an asymptomatic subclinical course to severe dengue shock syndrome. Besides, dengue can affect any organ in the body and can present with atypical manifestations. Case presentation: We report a 6-year-old previously healthy Tamil child who had dengue complicated with multiorgan involvement. She initially presented with high fever, headache, body aches for 5 days, blood and mucus diarrhea, hematuria, and right knee joint swelling for 2 days. Dengue NS1 antigen was positive on day 2 of febrile illness. She was managed symptomatically in the local hospital for 3 days and transferred to the tertiary care hospital for further management. She was eventually diagnosed as having dengue hemorrhagic fever complicated with multiorgan involvement including acute liver failure, pancreatic involvement, coagulopathy, arthritis, acute kidney injury, and multiple intracranial hemorrhages. The constellation of disease manifestations was identified as expanded dengue syndrome. She was managed with fresh blood, platelet, and cryoprecipitate transfusions and intravenous antibiotics in addition to renal and liver support in the intensive care unit. On day 14 of illness, she deteriorated while on the ventilator and died due to multiple intracranial hemorrhages. Conclusion: The reported child with dengue hemorrhagic fever developed several unusual presentations such as acute liver and renal failure, disseminated intravascular coagulopathy, pancreatic involvement, and multiple intracranial hemorrhages, which form part of expanded dengue syndrome. In the seriously unwell child, it is important to look for unusual complications actively to improve outcomes.Item Case Report: Dengue hemorrhagic fever with ischemic stroke.(American Society of Tropical Medicine and Hygiene, 2022) Basnayake, B.W.M.K.E.; Somaratne, K.G.S.K.; Goonetilleke, C.U.; Tilakaratna, P.M.Y.I.; Ranawaka, U.K.Several neurological manifestations are recognized in dengue infection, but stroke is a rare complication. We report a case of ischemic stroke in a patient with dengue hemorrhagic fever. A 52-year-old previously healthy male presented with a history of fever for 2 days, and left-sided weakness and numbness of sudden onset. MRI scanning showed a right-sided thalamic lacunar infarct. Diagnosis of dengue fever was made based on leuco-thrombocytopenia, positive dengue nonstructural protein-1 (NS-1) antigen, and positive dengue IgM antibodies. Severity of limb weakness correlated with the critical phase of dengue hemorrhagic fever (DHF). He was discharged home with good recovery from neurological symptoms and disability. Strokes are rare in dengue, and are mainly hemorrhagic strokes related to thrombocytopenia. Ischemic stroke is even rarer. More evidence is needed for confirmation of dengue as a pathogenic mechanism of ischemic stroke.