Conference Papers
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This collection contains abstracts of conference papers, presented at local and international conferences by the staff of the Faculty of Medicine
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Item Early hepatitis is the strongest risk factor for the development of severe dengue infection: A points-based risk-score to predict critical disease in dengue fever(Sri Lanka Medical Association, 2018) Niriella, M.A.; Udeshika, A.K.M.A.; Liyanage, I.K.; de Silva, A.P.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: Some dengue fever (DF) patients develop plasma leakage [critical-phase (CP)], which may progress to multi-organ failure. We attempted to identify early predictors ofCP in DF. METHODS: This was a retrospective, case-record-based study. Clinical, laboratory features in the first three-days (Dl-3) of illness was used to formulate a risk prediction model (RPM). Patients with serologically confirmed DF, admitted to the University Medical Unit, Teaching Hospital, Ragama, from 01.01.2017-30.06.2017 were included. Patients were randomly assigned to training (TD) and validation datasets (VD) of equal size. Stepwise multivariate logistic regression (p<0.05) was used to identify risk factors in TD. Versions of RPM were compared using Akaike criteria and McFadden's adjusted R2. Coefficients from the best RPM were used to derive weighted risk scores. Best RPM was validated in VD using C-statistic. RESULTS: 697 patients were included (mean-age:34.7±16.1 years, females-48.8%, TD=350, VD=346). CP developed inJ27 (32.6%). Mortality was I%. Risk predictors (p<0.05) were: female gender (OR=2.l), diabetes (OR=l.8), vomiting (OR=l.9), platelets60 IU/L (OR=3.3). In multivariate analysis, female gender (score=2), vomiting (score=3), platelets<120,000/mm-3 (score=3) and AST>60 IU/L 3 (score=4) were significant while diabetes was non-significant. Calculated RPM score ranged from 0-12. C-statistic for the TD was 0.78 and VD 0.77 (Hosmer-Lemeshow test: p=0.19 and 0.34 respectively). A cut-off of 5 was selected to maximise sensitivity (0.96), negative predictive value (0.95) with specificity of 0.44. CONCLUSION: This simple risk score seems useful in identifying those at risk ofCP within Dl-3 of the onset ofDF. The early presence of dengue hepatitis was the strongest predictor of CP.Item Predicting acute liver failure in dengue Infection(American Gastroenterological Association(AGA) Institute, Published by Elsevier Inc., 2013) Ranawaka, C.; Niriella, M.A.; Kumarasena, R.S.; Miththinda, J.K.N.D.; de Silva, A.P.; Premaratna, R.; de Silva, H.J.BACKGROUND: Dengue infections (DI) can range from being asymptomatic to severe illness. Unusual manifestations such as encephalitis, myocarditis, and acute liver failure (ALF) have been recognized. ALF is uncommon, but has a poor prognosis. The aim of this study was to identify predictors of ALF in DI. METHODS: Serologically confirmed patients with DI who were admitted to hospital from January 2009 to March 2010 were included. Patients consisted of direct admissions as well as referrals, some with deranged liver functions. Data was obtained from patient records. Clinical details and serum biochemistry was evaluated for up to five days from onset of illness. ALF in DI was defined as evidence of coagulation abnormality [International normalised ratio (INR) ≥ 1.5], and any degree of mental alteration (encephalopathy) in a patient without pre-existing cirrhosis. RESULTS: Out of 240 patients [57.7% male, 42.3% female; mean age 35.6 years (SD 15.4 years)], 164 had dengue with warning signs, 27 had dengue without warning signs and 49 had severe dengue. 15/49 severe dengue patients had profound shock. Abdominal pain, persistent nausea and vomiting (PNV), bleeding, hepatomegaly and ascites were present in 125, 92, 39, 129 and 28 cases respectively. Elevated aspartate aminotransferase (AST), serum bilirubin (SB), alkaline phosphatase (ALP) and gamma glutamyl transpeptide (GGT) were observed in 208, 20, 18 and 60 patients respectively. Of the 240 patients 41 had AST .1000 IU/ml (this included 4/ 15 with profound shock). 16/41 patients with AST .1000 IU/ml, including 4 with profound shock, developed ALF while none with AST ,1000 IU/ml developed ALF. In patients with AST .1000 IU/ml, presence of 2 or 3 of elevated SB, elevated ALP or PNV predicted the development of ALF with 93.8% sensitivity, 98.7% specificity, 83.3% positive predictive value and 99% negative predictive value (Fisher's exact test). CONCLUSIONS: Dengue patients with AST,1000 IU/ml are not at risk of developing ALF. Patients with AST .1000 (regardless of presence or absence of profound shock), with 2 or 3 of elevated SB, elevated ALP or PNV seem to be at risk of developing ALF. These findings need to be validated in a larger cohort of patients.Item Repeated dengue shock syndrome and "Dengue myocarditis" responding dramatically to a single dose methyl prednisolone(Sri Lanka Medical Association, 2012) Premaratna, R.; Rodrigo, K.M.D.; Anuratha, A.; de Alwis, V.K.D.; Perera, U.D.C.A.; de Silva, H.J.INTRODUCTION: Place of steroids in the management of severe dengue is unclear. A retrospective observational study appeared to show benefit of methylprednisolone (MP) in a highly selected group of patients. CASE REPORT: A 14-year-old schoolboy developed "myocarditis" (4th day) and on the fifth day, he collapsed with Dengue shock syndrome DSS needing rapid resuscitation with intravenous fluid boluses and dextran. He continued to have high fever (39-410C), and pulse rate (PR)>110/min and developed two further episodes of DSS and was resuscitated with further boluses of dextran. As there was no response with temperature 40.20C, PR 160/min, mid-arm systolic BP 70 mmHg, confused, restless, respiratory rate 36/min, dropping capillary 02 saturation, moderate pleural effusions and ascites, urine output <0.2ml/kg/Hr, made it extremely difficult to select the amount and type of fluid for resuscitation. Due to rapid deterioration a single dose of methylprednisolone (MP) (SOOmg in 200ml saline iv over 20 minutes) was administered as a rescue medication. He had deferversence within 30 minutes, became conscious and alert in 1 hour, PR reduced to 96/minute, BP remained stable above 100/80mmHg and urine output increased to 0.8-1.4ml/Kg/Hr. His ECG became normal after 3 hours, and the echo cardiogram in 12 hours (EF-55%). CONCLUSIONS: This patient with dengue developed three episodes of severe haemodynamic compromise within 12 hours while having third space fluid accumulation, "myocardits" and altered level of consciousness making it difficult to institute fluid therapy. A single dose of MP given as rescue measure resulted in a dramatic recovery suggesting a beneficial effect of MP in sever dengue.byItem Predictors of duration and degree 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: Fluid leakage is the hallmark of dengue shock syndrome. It is important to identify clinical and biochemical parameters which predict duration and degree of fluid leakage in dengue. METHODS: 102 patients with confirmed dengue were prospectively followed up for clinical, haematological and biochemical parameters, and they were correlated with ultrasonographic evidence of third space fluid accumulation (TSFA). RESULTS: Of the 102 patients (52 males; mean age 28.3 years(SD=11.8), TSFA was detected in 34/95(36%) after hospital admission; 33/95 had pleural effusions which included all except one of 21/95 who had ascites. 72.7% pleural effusions lasted 3 or more days and 52.4% ascites lasted less than 3 days. Duration of pleural effusion showed a significant positive correlation with maximum percentage rises of PCV (r=0.526,p=0.001) and Hb(r=0.525, p=0.001) and negatively correlated with WBC count (r=-0.361, p=0.020) and platelet count (r=-0.585, p=0.000). There was no correlation with any of the other parameters. The mean lowest WBC count of 3005/mm3that was recorded for patients who developed bilateral pleural effusions (n=21) was significantly less (p=0.042) than the mean lowest WBC count of 4091/mm3 that was detected for unilateral effusions(n=12). Duration of ascites was significantly positively correlated with highest AST(r=0.598, p=0.002) and highest ALT(n=0.721, p=.001. CONCLUSIONS: Maximum percentage rise of Hb and PCV, lower WBC and platelet counts seem to be associated TSFA. Among these, lower WBC counts appear to be more predictive of the degree of fluid leakage. Higher ALT and AST levels seem to be useful in predicting the duration of ascites.Item Predicting acute liver failure in dengue infection(Wiley Blackwell Scientific Publications, 2012) Ranawaka, C.K.; Kumarasena, R.S.; Niriella, M.A.; Miththinda, J.K.N.D.; Pathmeswaran, A.; Dassanayake, A.S.; de Silva, A.P.; Premaratna, R.; de Silva, H.J.BACKGROUND AND AIM: Dengue infections (DI) have a diverse clinical spectrum ranging from asymptomatic illness to severe dengue. Unusual manifestations such as encephalitis, myocarditis, and acute liver failure (ALF) are increasingly recognized. Though ALF is less common has a poor prognosis. Aim of this study was to identify possible predictors of ALF in DI. METHOD: Serologically confirmed patients with DI, admitted to university medical unit, Ragama, Sri Lanka from January 2009 to March 2010 were included. Patients were consisted of direct admission as well as referrals with deranged liver functions. Data was obtained from patient records. RESULTS AND DISCUSSION: Out of 240 patients (male : female 57.7%:42.5%; mean age 35.6 years [SD 15.4 years]), 164 had dengue with warning signs, 27 had dengue without warning signs and 49 had severe dengue. 15/49 severe dengue patients had profound shock. Abdominal pain, persistent vomiting (PV), bleeding, hepatomegaly and ascites were present in 125, 92, 39,129 and 28 cases respectively. Elevated AST/ALT, serum bilirubin (SB), alkaline phosphatase (ALP) and gamma glutamyl transpeptide (GGT) were observed in 208, 20, 18 and 60 patients respectively. Of the 240 patients 41 had AST/ALT > 1000 IU/ml and 199 had AST/ALT < 1000 IU/ml. Only 16/41 patients with AST/ALT > 1000 IU/ml developed ALF while none from the AST/ALT < 1000 IU/ml group. Only 4/15 of profound shock had ALF. Patients with AST/ALT > 1000 IU/ml, presence of 2 or 3 of; elevated SB, elevated ALP or PV predicted the development of ALF with 93.8% sensitivity, 98.7% specificity, 83.3% positive predictive value (PPV) and 99% negative predictive value (NPV) with p < 0.001. CONCLUSIONS: Dengue patients who’s AST/ALT < 1000 IU/ml, excluded patients at risk of ALF. Presence of 2 or 3 of: PV, elevated SB or elevated ALP in a patient with AST/ALT > 1000 IU/ml may indicate impending ALF. This needs further validation in a larger populationItem Early predictors of severe dengue in adults(Elsevier, 2012) Wijewantha, H.; Premaratna, R.; Mabharana, I.; Nishad, N.; de Silva, A.; de Silva, H.J.BACKGROUND: Dengue is the main infectious disease causing high morbidity and mortality among adults in dengue endemic regions of Sri Lanka. Prediction of severe illness at an earlier stage of infection helps to arrive at management decisions. Studies to identify predictors of severe dengue in adults are sparse. METHODS: In order to identify predictors of severe dengue by the third day of illness, symptoms, signs and investigation results of first 3 days of illness between two groups A and B (defined below) were compared in a prospective cohort study of consecutive 117 adult patients (age>12 years) with serologically confirmed dengue admitted to the professorial medical unit, Colombo North Teaching Hospital, Ragama, Sri Lanka over 6 month from 1st of March 2011. Group A (Severe illness): development of ascites or pleural effusions (evidence of fluid leakage), compensated shock and profound shock (as defined by WHO guidelines for Dengue 2010), Group B: all others who did not fall into Group A. Severity of symptoms was assessed by a visual analogue scale, and rest of the clinical parameters, investigation results were documented prospectively. RESULTS: Of the 117 adults (95 males) mean age 31.95years (SD=13.34); 27 fell into Group A and 90 into group B. On the 3rd day of illness, mean Aspartate aminotransferase (AST); Group A 260 iu/L (SD=168.8) vs Group B-145 iu/L (SD=135.11) (p=0.005). Mean Alanine aminotransferase (ALT); Group A-247 iu/L (SD=161.5) vs Group B-105iu/L (SD-91.5) (p=0.002). None of the symptoms, signs and other investigations including platelet count, packed cell volume (PCV) and white blood cell count was significantly different. Analysis of the whole 117, pearson correlation test showed a positive correlation of AST(r=0.3) (p=0.038) and ALT(r=0.3) (P=0.045) with PCV and a negative correlation (r=-0.3) with platelet count (p=0.014). AST(r=0.25) and ALT (r=0.3) on day 3 was positively correlated with development of malena at any stage (p=0.05). CONCLUSION: Higher AST and ALT levels on 3rd day of dengue seems to be useful predictors of severe dengue. © 2012 Elsevier Inc.Item Predictors of duration and degree of third space fluid accumulation in adult patients with dengue(Elsevier, 2012) Premaratna, R.; Ragupathy, A.; Miththinda, N.; de Silva, H.J.BACKGROUND: Fluid leakage is the hallmark of dengue shock syndrome. It is important to identify clinical and biochemical parameters which predict duration and degree of fluid leakage in dengue. METHODS: 102 patients with confirmed dengue were prospectively followed up for clinical, haematological and biochemical parameters parameters, and those were correlated with ultrasonographic evidence of third space fluid accumulation (TSFA). RESULTS: Of the 102 patients (52 males; mean age 28.3 years (SD 11.8), TSFA was detected in 34/95(36%) after hospital admission; 33/95 had pleural effusions which included all except one of 21/95 who had ascites. The majority of pleural effusions (72.7%) lasted 3 or more days and in most cases (52.4%) ascites lasted less than 3 days. Duration of pleural effusion showed a significant positive correlation with severity of body aches (assessed on a visual analogue scale) (r=0.523, p=0.001), maximum percentage rise of PCV (r=0.526, p=0.001) and maximum percentage rise of Hb (r=0.525, p=0.001). It was negatively correlated with WBC count (r= -0.361, p=0.020) and platelet count (r= -0.585, p=0.000). There was no correlation with admission weight (p=0.125), duration of fever (p=0.387), lowest pulse pressure (p=0.299), ALT(p=0.241), AST(p=0.328), average fluid intake per day (p=0.118) and fluid balance per day (p=0.129). The mean lowest WBC count of 3005/mm3 that was recorded for patients who developed bilateral pleural effusions (n=21) was significantly less (p=0.042) than the mean lowest WBC count of 4091/mm3 that was detected for unilateral effusions (n=12). There was no significant difference in other parameters between these 2 groups. Duration of ascites was significantly positively correlated with highest AST (r=0.598, p=0.002) and highest ALT (r=0.721, p=0.000). CONCLUSION: Severity of body aches on detecting effusions, maximum percentage rise of Hb and PCV, lower WBC and platelet counts seem to be associated with longer periods of TSFA. Among these, lower WBC counts appear to be more predictive of the degree of fluid leakage. Higher ALT and AST levels seem to be useful in predicting the duration of ascites. © 2012 Elsevier Inc.Item To identify the role of haemoglobin (Hb), pack cell volume (PCV) and pulse pressure (PP) in predicting fluid leakage in patients with dengue who consume adequate amounts of fluids(Elsevier, 2012) Premaratna, R.; Ragupathy, A.; Miththinda, N.; de Silva, H.J.BACKGROUND: Early detection of fluid leakage is important in identifying patients who are likely to develop shock syndrome in dengue. As patients with dengue are advised to consume adequate amounts of fluids such behaviours may alter the clinical and haematological parameters predicting fluid leakage. METHODS: In 102 confirmed dengue patients admitted to Professorial Medical Unit, Colombo North Teaching Hospital Ragama from September 2011,quantity and quality of fluids consumed, Hb, PCV, PP and their percentage rise or decline were documented and compared between those who developed and did not develop moderate third space fluid accumulation (3rdSFA) [either pleural effusions, ascites or both detected by ultrasonography. RESULTS: In 102 patients (52 males) with mean (SD) age 28.3 (11.8) years, 3rd SFA was detected in 7/102 (6.8%) on admission and 34/95 (37%) after admission. Compared with those who had 3rdSFA and did not have 3rdSFA at admission; average consumption of water 1044cc/day vs 1091cc/day (p=0.8) and solutes 1050cc/day vs 805cc/day (P=0.26); the mean(SD) Hb 14.7 (2.0) g/dl vs 13.6 (1.8) g/dl (p=0.1); PCV 43.8 (6.5) vs 41.2 (5) (p=0.19); mean pulse pressure 32.8mmHg vs 33.8 (p=0.76). In those who developed 3rdSFA and did not develop 3rdSFA after admission, average consumption of water 620cc/day vs 491cc/day (p=0.14); solutes 1461cc/day vs 1481cc/day (p=0.83); the highest mean (SD) Hb 14.66g/dl (1.82)g/dl vs 14.28 (1.6)g/dl (p=0.3) and highest mean(SD) PCV 44.16 (5.19) vs 43.4 (4.5) (p=0.46); the mean (SD) pulse pressure 29.9mmHg vs 28.4 (p=0.29); The maximum percentage rise in Hb 8% vs 4.6% (p=0.02); PCV 8.6% vs 4.5% (p=0.006); mean pulse pressure drop 6.9% vs 5.9% (p=0.84). CONCLUSION: In the presence of fluid consumption the quality or quantity of fluids consumed did not seems to have played a role in 3rdSFA. A single value of Hb, PCV or pulse pressure was not helpful in predicting early fluid leakage. While percentage reduction in pulse pressure was not helpful, percentage rise in Hb and PCV remained predictive of early fluid leakage in dengue. © 2012 Elsevier Inc.Item Co-existence of double serotypes of dengue in patients of Gampaha District(Sri Lanka Association for the Advancement of Science, 2007) Jayasooriya, D.; Gunawardene, Y.I.N.S.; Hapugoda, M.D.; Premaratna, R.; Manamperi, A.; de Silva, H.J.; Abeyewickreme, W.Dengue virus (DENV) known to cause a productive cytolytic infection in humans exists in four different serotypes Dengue 1 (D1), Dengue 2 (D2), Dengue 3 (D3) and Dengue 4 (D4). Among 4 serotypes of DENV, D 3 thought to be associated with explosive DHF epidemics and severe disease in many countries. Our objective was to determine the prevalence of dengue serotypes in Gampaha District and to correlate them with disease severity. Serum samples were collected from patients who were within 4 days of onset of fever and clinically suspected of dengue according to WHO criteria. Total viral RNA extracted from each serum sample was subjected to RT-PCR followed by a semi-nested PCR using specific primers. Out of 91 samples collected between Nov 2005 and Dec 2006, 16 samples were confirmed positive for DENV RNA by RT-PCR. Our results of multiplex semi-nested PCR indicated that 9/16 (56.25 %) of the positive cases were co-infected with serotype 2 and 3 (D2 & D3), while 4/16 (25%) were infected with D 3 and 3/16 (18.75 %) with D 2. 3/4 of D 3 cases had DHF , 1/3 of D2 cases were DHF while there were no DHF cases among the D2 and D3 co-infected patients. The mean Packed cell Volume (PCV) values of D3, D2 and D2 & D3 co-infected were 53.8 %, 48 % and 39.6% respectively while the mean platelet values of those were 66,000 mm3, 123,000 mm3 and 174.000 mm3 , respectively. Dengue infection by a single serotype is common among patients. Although few cases of co-infection by more than one serotype had been previously reported in a few other countries, this is the first description of simultaneous co-infection by D2 and D3 in Gampaha district. In this limited study we have observed a reduction of disease severity in D2 and D3 simultaneously co-infected patients. Could simultaneous co-infection by more than one serotype or a combination of two particular serotypes have lead to a decrease in disease severity among dengue patients is a matter yet to be studied. Further studies are needed to support these conjectures and to establish the clinical implications of simultaneous co-infection on the prevalence of DHF and disease severity. Acknowledgement: NSF (grant SIDA/2006/BT/02) & IAEA (SRL TC 6/028)Item Aedes albopictus the “underrated” Asian Tiger(University of Kelaniya, 2010) Jayasooriya, D.H.S.W.; Gunawardene, Y.I.N.S.; Manamperi, A.; de Silva, H.J.; Abeyewickreme, W.Introduction The mosquito Aedes aegypti was thought to be the main vector responsible for virtually all dengue epidemics; while Aedes albopictus was considered a vector in which the virus is maintained but does not cause epidemics. Objective The study was conducted covering three endemic districts in Sri Lanka to determine the role of genus Aedes during dengue transmission. Methods and Material Mosquitoes were collected within a 350m radius from the location of the positive patients. Heads and abdomens of 63 pools were tested for DENV RNA with and RT-PCR-LH-(P32) assays Results Discussion Ae. albopictus was present in majority of the locations in all districts surveyed. Ae. albopictus was found in 13/17 (76.47%), 24/25 (96%)and 19/22 (86.36%) sites in Colombo, Gampaha and Kurunegala respectively. The RT-PCR-LH-(P32) assays indicated that 5/25 (20%) sites in Gampaha, 2/17 (11.76%) in Colombo and 6/22 (27.27%) in Kurunegala were positive for DENV. In Gampaha and Colombo there were 3 and 1 of DEN-2 positive pools respectively, while there were 2 and 1 of DEN-3 positive pools respectively. A higher number of positive pools (4/1or 21.05%) for DEN-1 and 1/1(5.26 %) for DEN-4 were found in Kurunegala. In Kurunegala one pool was positive for both DEN-2 and DEN-4 indicating the circulation of multiple serotypes within close proximity. Moreover one of the three DEN-2 positive pools in Gampaha consisting of only male Ae. albopictus mosquitoes is supportive of the belief of vertical transmission of DENV. In a DEN-4 positive location in Kurunegala HI was found to be10%, BI= 1and CI= 5.88 %while anotherDEN-2 positive site in Wattala showed HI of 5.55%and a BI of 5.55 suggesting active transmission. The abundance of Ae. albopictus in all districts and the findings indicating that100% of the positive pools were made of Ae. albopictus in this study highlights the importance of Ae. albopictus in the transmission dynamics dengue. The ability of Ae. albopictus to be infected with low viremia and the degree to which it permits replication within the mosquito itself could have an impact on the transmission and these verity of the disease. Co-circulation of two or more serotypes in a single pool or in different pools of mosquitoes within the same district is suggestive of hyper endemic transmission dengue in the three districts. The greater susceptibility of Ae. albopictus to infection by DENV is said to lead to greater virus adaptation. Sri Lanka as a whole would be at serious risks for multiple outbreaks in future. Our results indicate that Ae. albopictus is more efficient in dengue transmission than previously thought. The results shed light on the efficiency of Ae. albopictus as a vector in transmitting DENV in the absence or low abundance of Ae. aegypti in Sri Lanka. The present study suggests that Ae. albopictus sp is underrated in terms of transmission potential during peak transmission periods of dengue in Sri Lanka. Key words: RT-PCR-LH-(P32) RT-PCR-Liquid Hybridization with P32 radio isotope, HI-House hold Index, BI- Breteau Index, CI-Container Index,DENV-Dengue Virus Authors wish to acknowledge the financial assistance rendered by the NSF Sri Lanka (GrantNo:SIDA/2006/BT/02)and the IAEA (Grant NoTC SRL 6/028).