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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Dengue and leptospirosis infection during the coronavirus 2019 outbreak in Sri Lanka(Oxford University Press, 2021) Niriella, M.A.; Ediriweera, D.S.; de Silva, A.P.; Premaratna, B.A.H.R.; Jayasinghe, S.; de Silva, H.J.ABSTRACT: A significant decrease in dengue fever cases and a contrasting increase in leptospirosis cases were reported for the second quarter of 2020 compared with 2019 in Sri Lanka. In the absence of significant environmental and weather-related differences to account for these changes in incidence, we investigated the possibility that the effects of the COVID-19 pandemic on public health, social behaviour and the restrictions imposed during the lockdown influenced the fluctuations in dengue and leptospirosis infections. KEYWORDS: COVID-19; dengue fever; leptospirosis; pandemic; tropical infections.Item 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 Clinical and virological features of dengue in 2010(Sri Lanka College of Microbiologists, 2011) Hapugoda, M.D.; Manamperi, H.; Gunasena, S.; Athapaththu, A.M.M.H.; Premawansa, G.; Wellawaththage, C.; Jayarathna, T.D.S.S.; Abeyewickreme, W.INTRODUCTION: Dengue is an important viral infection in Sri Lanka. All 4 serotypes co-circulate in Sri Lanka. OBJECTIVE: To study the clinical and virological features of dengue in 2010. DESIGN, SETTING AND METHODS: A hospital-based study was carried out at North Colombo Teaching Hospital, Ragama in 2010. Patients clinically suspected of having dengue, with fever less than 5 days were recruited. Acute and convalescent blood samples were collected within 7 days after obtaining informed written consent. Demographic, clinical information and laboratory results were obtained. Acute serum samples were tested using molecular (RT-PCR and Semi-Nested PCR) and serological (ELlSAs and HAI) assays. Convalescent samples were tested by serological assays. RESULTS: Of 209 patients enrolled, 93 % (195/209) were laboratory confirmed as recent positive cases of dengue viral infection; of these, 5% (9/195) were classified as dengue fever; 85%(1G5/195) dengue haemorrhagic fever (DHF) and 0.5% (1/195) dengue shock syndrome. Mean platelet value and packed cell volume (PCV) in laboratory confirmed dengue patients were 56,107/mm3 (range 10,000-306,000) and 42%(range 34-61 %) respectively. Patients infected with DHF showed both primary (n=45) and secondary (n=102) infections. Interestingly, secondary infection was not significantly correlated with DHF (x2-0.3:p=0.6). DEN-1 was responsible for the majority of cases, with a minority due to other three serotypes; all serotypes contributed to severe disease. CONCLUSION: DEN-1 was responsible for the majority of cases in 2010 but it circulated at a low level during previous epidemics. Majority of patients had severe clinical symptoms. In this epidemic, the clinical presentation of dengue differed according to the geographic region and viral serotype. ACKNOWLEDGMENTS: Financial assistance and technical co-operation by International Center for Genetic Engineering and Biotechnology (ICGEB CRP SRL 08/02), National Science Foundation (NSF/RG/2009/BT/01) and International Atomic Energy Authority (lAEA/SRL/5/042) is acknowledged.Item Molecular and entomological studies on dengue(Faculty of Medicine, University of Kelaniya, Sri Lanka, 2016) Hapugoda, M.A novel molecular-based assay (Reverse Transcription-Polymerase Chain Reaction-based Liquid Hybridization (RT-PCR-LH)) was developed and validated for early detection of dengue virus in clinical specimens. Possible risk factors affecting transmission of dengue were studied in dengue hot-spots. Soluble fragment of dengue virus in clinical samples were sequenced and gene and protein sequences were compared with available sequences. The novel assay was found to be more sensitive than the other diagnostic techniques for early and definitive laboratory diagnosis. Further, the assay could detect dengue virus in field-caught Aedes albopictus specimens. Ae. albopictus acts as an important vector of dengue in some urban and semi-urban areas. Some socio-ecomonic and other factors directly affect transmission of dengue in the hot-spot. Risk maps developed in the study are important to predict impending dengue epidemics so that limited resources could be utilized in a cost effective manner to control the disease. Sequence analysis of dengue virus indicated that dengue 2 serotype of Indian ancestry had been introduced to Sri Lanka. All districts in Sri Lanka were hyperendemic to dengue with signs of rapid rate of in situ evolution of dengue 3 serotype.Item A study to determine quantitative predictors for development of third space fluid accumulation in adult patients with dengue(Sri Lanka Medical Association, 2012) Premaratna, R.; Ragupathy, A.; Miththinda, J.K.N.D.; de Silva, H.J.INTRODUCTION: Prediction of severe illness remains the most important measure in preventing mortality associated with dengue. Increased vascular permeability leading to reduced intravascular volume is the hallmark of dengue shock syndrome. Third space fluid accumulation (TSFA) reflects severe vascular permeability and therefore, it is important to quantitatively identify parameters which predict the occurrence of TSFA in dengue. METHODS:102 patients with confirmed dengue were prospectively followed up for clinical, haematological, biochemical parameters and for evidence of TSFA by serial utrasonography. These parameters were tested against development of TSFA using Receiver Operating Characteristic [ROC] curves to identify quantitative predictors of development of TSFA. RESULTS: 102 patients (52 males) with mean age 28.3 years (SD 11.8), TSFA was detected in 34/95 [36%) after admission; 21/95 developed ascites at mean 5.7 days of illness (SD 1.3) and 33/95 had pleural effusion at 5.4 days (SD 1.5). Onset of TSFA could be identified using percentage rises of highest PCV (p= 0.002) where 6.5% rise of PCV predicted TSFA(sensitivity 61%, specificity 62%)], highest Hb (p=0.017) where rise of 6.1% in Hb predicted TSFA (sensitivity 55%, specificity 64%), lowest recorded platelet count (p<0.000) where platelet count of 48500/mm3 or less predicted TSFA (sensitivity of 83%, specificity 51) post-admission fluid input-output balance per day (p 0.002) where positive balance more than 777cc/day predicted TSFA (sensitivity 65%, specificity 64%). CONCLUSIONS: Rise of PCV and Hb, platelet count, WBC count and daily fluid balance appear to be useful quantitative predictors of TSFA in dengue.Item Developing a severity index on day 4 to predict severe dengue infection in adults(Sri Lanka Medical Association, 2012) Wijewantha, H.S.; Premaratna, R.; Nishad, A.A.N.; Mabharana, I.D.M.; de Silva, A.P.; Waraketiya, P.R.; Niriella, M.A.; de Silva, H.J.INTRODUCTION: Dengue causes high morbidity and mortality among adults in Sri Lanka. Early prediction of severe illness would help to reduce morbidity and mortality. Studies to identify predictors of severe dengue in adults are sparse. AIMS: To identify predictors of severe dengue infection by the fourth day of illness. Methods: Symptoms, signs and investigation results on the 4th day of illness were compared between two groups of patients with serologically confirmed dengue over 6 months from 1st of March 2011; Group A (severe illness: evidence of fluid leakage, compensated shock, profound shock). Group B (non-severe illness). RESULTS: Of 117 adults 9meanage 32 yrs (SD= 13.3) and 95 males) 27 fell into Group A and 90 into group B. On day 4 of illness serum aminotransferases (AST and ALT) were significantly higher in Group A than group B [AST: 260 iu/1 (SD=168.8] vs 145 iu/l(SD 135.11), p=0.005; ALT: 247 iu/1 (SD= 161.5) vs 105 iu/1 (SD= 91.5), p=0.002]. Overall AST (r=0.3, p=0.038) and ALT (r=0.3, p=0.045) had a positive correlation with haematocrit (PCV). An index was developed using stepwi-se multivariate discriminant function analysis to predict severe infection by the 4th day. A severity Index, [(0.082 x PCVD4) + (0.02 x PlateIetD4) + (-0.006 x ASTD4) -3.677] of <-0.258 predicted severe infection with 73.7 % specificity, 73.8% sensitivity, 56% positive predictive value and 86% negative predictive value. CONCLUSIONS: A severity index <-0.258 calculated on the 4th day of illness may predict severe infection among adult dengue patients. This must now be validated prospectively.Item Viral characteristics and genomics of early onset, single organ specific presentations in dengue(Sri Lanka Medical Association, 2013) Premaratna, R.; Perera, H.K.K.; Chan, K.H.; Yeung, M.F.; Mettananda, C.; Peiris, J.S.M.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: Early onset neurological, hepatic and cardiac complications of dengue are increasingly recognized. However, doubts exist as to whether such complications of dengue are consequences of dengue shock syndrome rather than direct organ involvement. We studied virus characteristics and their genomics in patients who presented with early onset single organ involvement due to dengue, without features of DSS. METHODS: Blood samples were collected at admission of seven patients, who presented to the Professorial Medical Unit, Colombo North Teaching Hospital Ragama during 2011-2012, confirmed as having acute dengue by PCR. Samples were analysed with single-tube, nested RT-PCR using type-specific primers. Viral RNA was extracted and sequencing was performed. The dengue virus sequences were aligned with other sequences that are available in the GenBank and maximum-likelihood (ML) tree was made. RESULTS: Early onset organ specific manifestations included; self-limiting fits and clouding of consciousness on the 2nd day, rise in AST (1337iu/L) and ALT (749iu/L) on the 4th day and T wave inversions in the ECG on the 3rd day. Seven Dengue 1 viruses were isolated, which were in close homology in all 7 patients, based on the maximum likelihood tree with 1000 boot-straps. CONCLUSIONS: All the strains detected were clustered within the Genotype I clade of dengue-1 and in close homology with the dengue-1 viruses detected in the country in the recent past. The significance of viral characteristics and genomics related to organ specific manifestations need further study.Item Effectiveness of single dose intravenous methyl prednisolone in reversing on going vascular leakage in dengue(Sri Lanka Medical Association, 2013) Premaratna, R.; Abeyrathna, C.; de Alwis, K.; de Silva, H.A.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: Non-resolution of vascular leakage within 48 hours in dengue shock syndrome (DSS) can result in complications in the recovery phase due to fluid overload. It can also result in death in 0.5-5%. No medication is known to reverse the ongoing vascular leakage. METHODS: Single dose intravenous methyl prednisolone (SDIVMP) was administered to 11 consecutive PCR confirmed adult patients who had ongoing high fever on the 5th day of illness and evidence of plasma leakage; significant rise in Hb, PCV, AST levels and confirmation of fluid leakage by ultrasonography. Informed written consent was obtained from all patients prior to administering SDIVMP. RESULTS: 7/11 were males. Mean age was 24 years (SD 8). At the time of administering SDIVMP; median rise of Hb 9% (5-12), PCV 12%(10-19), absolute rise of AST from 56 iu/L(24-68) to 678iu/L (320-1034) and drop in platelets from 123xl09/L (96-165) to 32xl09/L (15-56). After administration of SDIVMP in all patients, fever reduced rapidly within one hour and there was no further clinical deterioration, rise in Hb, PCV, AST or worsening of ascites or pleura! effusions. However in 5 patients platelet counts continued to drop to < 10x10 /L over the next 2-3 days. None of the patients developed sepsis, abnormal sugars or any other complications such as sepsis, or abnormalities in glucose control. CONCLUSIONS: SDIVMP was effective in reversing fluid leakage in dengue. These findings support the conduct of a double blind placebo controlled trial.Item Knowledge and practices of dengue control and their effect on breeding sites and vector populations(Sri Lanka Medical Association, 2010) Pinidiyapathirage, M.J.; Gunethilake, M.A.G.N.; Wijegunawardana, N.D.A.D.OBJECTIVE: To describe the association between knowledge and practices of dengue control with the observed dengue breeding sites and vector populations in a community. METHODS: A cross-sectional survey was conducted among households in Negombo area in July 2009 during the height of the dengue epidemic in the country. Knowledge and practices in this community were measured using two methodologies. The first was a questionnaire, to be answered by the household respondent; the second, a mosquito larval survey, to identify potential and actual mosquito breeding sites in the corresponding household. The use of the two instruments allowed comparison of respondent knowledge and reported practice with the actual condition of the compound. RESULTS: All respondents (n=120) have heard of dengue, 89% knew at least one symptom of dengue and 93% knew that a mosquito was responsible for transmission. 60% correctly stated the preferred biting times of the vector and 80% knew that discarded tyres, bottles and plastic containers with water collections were the potential vector breeding sites. On inspection, 104 (87%) households had at least one potential breeding source. However, Aedes aegypti/albopictus larvae/pupae were observed only in water samples collected from 3 (2.5%) households. Knowledge about dengue symptoms, methods of prevention or level of education had no association with the potential breeding sites found. Low income was significantly associated with having at least one potential breeding source in the household. CONCLUSION: Although the level of knowledge about dengue was high in this community, we found only httle evidence that this knowledge was put into practice.