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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Predictive value of hepatic transaminases during febrile phase as a predictor of a severe form of dengue: analysis of adult dengue patients from a tertiary care setting of Sri Lanka(Biomed Central, 2021) Priyangika, D.K.D.; Premawansa, G.; Adikari, M.; Thillainathan, S.; Premawansa, S.; Jayamanne, B.D.W.; Premaratna, R.OBJECTIVES: Dengue viral infection is an ongoing epidemic in Sri Lanka, causing significant mortality and morbidity. A descriptive-analytical study was carried out using serologically confirmed Dengue patients during a 6-month period. The relationship between the elevation of hepatic enzymes and severity of Dengue was assessed after stratifying recorded maximum AST/ALT (SGOT/SGPT) values 2-15 times elevated and by the phases of the illness. Sensitivity, specificity, predictive values, and ROC curves were assessed using maximum values for AST and ALT. RESULTS: Out of 255 patients, 107(42%) were females. The majority (52.9%) were in the 20-39-year age group. Only 19.6% had DHF. No statistically significant difference was noticed in the values of maximum transaminases during the febrile phase among DF and DHF patients. Higher sensitivity and low specificity with the 1-5 times elevation range was noticed, and a higher cut-off level of more than 5 times elevation showed low sensitivity and higher specificity. The combination of both transaminases cut-offs with age and sex also does not show clinically significant predictability of severe disease. The AST and ALT elevations are not showing discriminatory predictive value on dengue severity. As different serotypes cause different epidemics, it is important to carry out large-scale specific studies considering the serotypes. KEYWORDS: And liver enzymes; Dengue; Dengue severity prediction; Transaminases in Dengue.Item Expression of Nitric Oxide synthase and Nitric Oxide levels in peripheral blood cells and oxidized low-density lipoprotein levels in saliva as early markers of severe dengue.(Hindawi, 2021) Hapugaswatta, H.; Ruwani, L.; Wimalasekara; Perera, S.S.; Premaratna, R.; Seneviratne, K.N.; Jayathilaka, N.BACKGROUND: Severe dengue (SD), experienced by only a fraction of dengue patients, can be lethal. Due to the lack of early markers that can predict the evolution of SD, all dengue patients have to be monitored under hospital care. We discovered early oxidative stress markers of SD to identify patients who can benefit from early intervention before the symptoms appear. METHODS: The expression of inducible nitric oxide synthase (iNOS) in peripheral blood cells (PBC), nitric oxide (NO), and oxidized lowdensity lipoprotein (oxLDL) levels in plasma and saliva collected at early stages of dengue infection from 20 nonsevere dengue fever (DF) patients and 20 patients who later developed SD were analyzed in a retrospective nested case-control study. RESULTS: The expression of iNOS is significantly (P < 0:05) lower in patients who developed SD than in DF patients at admission within 4 days from fever onset. Median plasma NO concentration within 4 days from fever onset is also significantly (P < 0:05) lower in patients who developed SD (17:9±1:6 μmol/L) than DF (23:0±2:1 μmol/L). Median oxLDL levels in plasma within 3 days from fever onset is significantly (P < 0:05) lower in patients who developed SD (509:4 ± 224:1 ng/mL) than DF (740:0 ± 300:0 ng/mL). Median salivary oxLDL levels are also significantly (P < 0:05) lower in patients who developed SD (0:8±0:5 ng/mL) than DF (3:6±2:6 ng/mL) within 4 days from fever onset. CONCLUSIONS: These findings suggest that the expression of iNOS (73% sensitivity, 86% specificity) and plasma NO (96% sensitivity, 61% specificity at 22.3 μmol/L; P < 0:05) may serve as early markers of SD within 3 days from fever onset. Salivary oxLDL levels may serve as early noninvasive markers of SD with a sensitivity and specificity, respectively, of 57% and 91% at 0.9 ng/mL; 76% and 55% at 2.3 ng/mL; and 100% and 50% at 4.6 ng/mL (P < 0:05) within 4 days from fever onsetItem 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 Silent transmission as a risk factor affecting transmission of dengue fever.(Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, 2007) Hapangama, H.A.D.C.; Hapugoda, M.D.; Gunawardene, Y.I.N.S.; Premaratna, R.; Dayanath, M.Y.D.; Abeyewickreme, W.The global incidence of dengue fever has increased by more than four-folds over the last 30 years, making it the most threatening mosquito-borne viral disease at present. Objective of this study is to determine the role of silent transmission •on' incidence of dengue. A total of 40 households, living within a 300 m radius of seven selected ‘confirmed dengue cases at different dengue high risk localities in Gampaha District were recruited for this study. A minimum of three inhabitants were tested for anti-dengue antibodies using a commercial kit to determine the prevalence of silent transmission on dengue infection in each households. Entomological surveillance was carried out in all seven localities. Out of 40 households, 26 (65%) houses were positive for dengue viral infection. Total of 148 inhabitants (68 Males); mean age; 35.9 years were enrolled. Of the 148, 41 (27.7%) had evidence of exposure to dengue virus [positive for IgM: 28/41(68.4%), IgM'& IgG: 7/41(17%) and IgG: 6/41(14.6%)]. Out of 28 primary infections, 20(71.4%) were asymptomatic. Of the 7 secondary infections, 1(14.28%) was asymptomatic. Of the 6 previous exposures to dengue 4(66.67%) were asymptomatic. Of the 7 localities investigated, 1 had >50%, 4 had >25% and 2 had <25% clustering of cases. Ae. albopictus found in all seven localities and Ae. aegypti found only in two localities. This study suggests presence of silent transmission of dengue virus with a trend towards clustering around cases and also this shows that the presence of vectors increases the incidence of dengue.Item Dengue as-a public health problem in Sri Lanka(La Fondation pour l’Université de Lyon, 2009) Hapangama, H.A.D.C.; Gunawardene, Y.I.N.S.; Hapugoda, M.D.; Premaratna, R.; Manamperi, A.; Gunasena, S.; Abeyewickreme, W.Dengue infection is an important global public health problem and an increasing number of persons from the South Asian region have been directly or indirectly affected by the disease. In Sri Lanka, dengue has become a major threat to public health in many urban and sub-urban' areas during past three decades. Rapid unplanned urbanization and increasing human population has increase the rate of infection and the frequency. The study area, Gampaha District is the second most populous district in the country having a population density of 1 539 persons per km2 and was the district reporting the second highest incidence of dengue in 2008. Therefore, current research efforts are focused on dengue transmission, examining the presence of sub-clinical infections, role of vector mosquitoes and Knowledge, Attitude and Practices (KAP) of the community on dengue infection in an effort to contain the disease. In the present study, dengue antibodies were detected in samples collected from clinically suspected patients and as well as in samples collected from volunteers. Volunteer sera collected around the confirmed cases had a 23.6% sero-positive rate for dengue IgM antibodies. The rate of asymptomatic recent infections was calculated to be 16.9%. In present study we have serologically confirmed the presence of subclinical infections and according to the published data this is the first confirmation of asymptomatic dengue infections in Sri Lanka. According to the entomological investigations carried out, the common breeding places for Aedes vectors were found to be discarded small containers. Even though Ae. Aegypti has been considered as the principal vector transmitting dengue fever, current studies highlighted the predominant ro!e of Ae. albopictus in the disease transmission. A previous study in Sri Lanka also suggested that prevalence and .presence of high-density of Ae. albopictus should be considered as a risk factor for endemic/epidemic dengue. In view of the above, the spread of dengue by Ae. albopictus should be a matter of great concern. Findings of KAP survey revealed that the community possessed substantially higher knowledge on the spread of dengue, vectors, vector breeding and also seriousness of the infection. However it was observed that good knowledge does not necessarily lead to good practices. Since the attitudes of the respondents were found to be good and most of them were supportive of control measures; next effort of the present study is to see how a novel community mobilized solid waste management system will be effective in dengue vector control.Item 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.