Browsing by Author "Rajapakse, S."
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Item Cardiac emergencies in obstetrics(Taylor and Francis Group, 2021) Padumadasa, S.; Rajapakse, S.No abstract availableItem A case of hypotension and heart rate changes on rechallenge with a low dose of clozapine with no apparent secondary cause(Sri Lanka College of Psychiatrists, 2022) Harshini, M.L.; Fernando, A.I.W.; Abayawickrama, H.M.T.S.; Ikram, M.I.N.; Rajapakse, S.; Hapangama, A.Clozapine is known to cause innocuous as well as severe and or fatal cardiovascular side effects. These side effects are commonly reported at the initiation of clozapine therapy. We report a patient who was stable on clozapine for several years but in whom we had to withhold clozapine for medical reasons and subsequently developed significant hypotension and heart rate changes when rechallenged with a small dose of clozapine.Item Changes in full blood count parameters in leptospirosis: a prospective study(BioMed Central, 2014) de Silva, N.L.; Niloofa, M.; Fernando, N.; Karunanayake, L.; Rodrigo, C.; de Silva, H.J.; Premawansa, S.; Handunnetti, S.M.; Rajapakse, S.BACKGROUND: Leptospirosis presents diagnostic challenges to clinicians, in settings where other acute febrile illness are prevalent. The patterns of serial changes in haematological parameters in leptospirosis has not been evaluated previously. METHODS: Clinical and laboratory data were collected prospectively from patients with leptospirosis in two hospitals in Sri Lanka. Leptospirosis was diagnosed based on WHO clinical criteria with confirmation using Microscopic Agglutination Test titre > 400 or 4 fold rise between acute and convalescent samples. Full blood count parameters were analysed up to the 14th day of illness. RESULTS: Data from 201 patients with leptospirosis were available. Leukocyte counts and absolute neutrophil counts showed a decline over the first 5 days of illness, then rose until the end of the second week. On day 3 of fever, the majority (75%) had normal leukocyte counts, and by day 5, leukocytosis was seen only in 38.1%; leucopenia was an uncommon finding. Lymphopenia was seen in over half on day 5, declining to just under a quarter of patients by day 10. Platelets declined over the first 6 days and then gradually rose. Thrombocytopenia was seen in nearly three-fourths of patients by day 5. Haemoglobin and haematocrit levels declined over the course of illness. Total white cell and neutrophil counts were higher, and haemoglobin and haematorcrit were significantly lower, in patients with severe disease. CONCLUSIONS: Neither leukocytosis nor lymphopenia were prominent features, while thrombocytopenia was seen during the 3rd to 5th day of illness, with dropping haemoglobin levels. Neutrophilia and low haemoglobin levels appear to predict severe disease. These findings may be of use to clinicians in differentiating leptospirosis from other acute infections like dengue, and could help in predicting severe leptospirosis.Item Clinical and laboratory associations of severity in a Sri Lankan cohort of patients with serologically confirmed Leptospirosis - a prospective study(Sri Lanka Medical Association, 2015) Rajapakse, S.; Weeratunga, P.N.; Rodrigo, C.; Sriharan, S.; Niloofa, M.J.R.; Fernando, N.; de Silva, H.J.; Karunanayake, L.; Premawansa, S.; Handunnetti, S.INTRODUCTION AND OBJECTIVES: Leptospirosis is a zoonotic infection of significant morbidity and mortality. This study elucidates the markers of severity in a cohort of Sri Lankan patients with serologically confirmed leptospirosis. METHOD: Prospectively recruited patients presenting to three healthcare institutions in the Western province of Sri Lanka with serological confirmation of leptospirosis with the microscopic agglutination test were included. Data regarding the socio-deruographic profile, clinical presentation, complications and biochemical parameters were recorded. Univariate associations and subsequent multivariate logistic regression models were constructed with severity as the dependent variable. RESULTS: A total of 232 patients were included. Majority were male (86.6%). Severe disease was noted in 68.5%. Significant clinical associations of severe disease included fever > 38.8°C on presentation (p=0.008), age>40 yrs; (p = 0.033), muscle tenderness (p=0.04) and tachycardia on admission (p=0.05). Laboratory associations of severe disease were highest white cell count > 12,350/mm3 (p<0.001) and < 7900/mm3 (p = 0.009), highest neutrophil percentage > 84% {p < 0.001). Hemoglobin > 11.2g/dL (p<0.001) and < 10.2 (p<0.001), packed cell volume > 33.8% (p <0.001) and <29.8% (p <0.001), lowest platelet count <63,500/mm3 (p = 0.01), highest ALT > 70 IU/L {p = 0.02) and hyponatremia with sodium <131mEq/L (p=0.004) On multivariate analysis, PCV < 29.8 (P = 0.011; adjusted OR =3.750; Cl = 1.394 - 10.423), ALT >70 P =0.044 adjusted OR =2.639; Cl =1.028-6.774 and hyponatremia< 131 (p=0.019 adjusted OR=6.413; Cl=1.353 -30.388) were found to be independent associations of severe disease. CONCLUSION: Severity associations were demonstrated with both clinical and laboratory parameters.Item Clinical and laboratory associations of severity in a Sri Lankan cohort of patients with serologically confirmed leptospirosis: a prospective study(Oxford : Oxford University Press, 2015) Rajapakse, S.; Weeratunga, P.; Niloofa, M.J.; Fernando, N.; Rodrigo, C.; Maduranga, S.; de Silva, N.L.; de Silva, H.J.; Karunanayake, L.; Handunnetti, S.BACKGROUND: Leptospirosis results in significant morbidity and mortality. This study elucidates markers of severity in a cohort of Sri Lankan patients. METHODS: Patients presenting to three healthcare institutions in the Western province of SriLanka with leptospirosis serological confirmed by the microscopic agglutination test (MAT) were included. Prospective data regarding demographic, clinical and laboratory parameters was extracted. Univariate associations and subsequent multivariate logistic regression models were constructed. RESULTS: The study included 232 patients, with 68.5% (159) demonstrating severe disease. Significant associations of severe disease at a significance level of p<0.05 were fever >38.8°C on presentation, age >40 years, muscle tenderness, tachycardia on admission, highest white cell count >12 350/mm(3) and <7900/mm(3), highest neutrophil percentage >84%, haemoglobin >11.2 g/dL and <10.2 g/dL, packed cell volume (PCV) >33.8% and <29.8%, lowest platelet count <63 500/mm(3), highest alanine transaminase (ALT) >70 IU/L and hyponatremia with sodium <131mEq/L. On multivariate analysis, PCV <29.8% (p=0.011; OR 3.750; CI: 1.394-10.423), ALT >70 IU/L (p=0.044; OR 2.639; CI: 1.028-6.774) and hyponatremia <131mEq/L (p=0.019; OR 6.413; CI: 1.353-30.388) were independent associations of severe disease. CONCLUSIONS: Severity associations were demonstrated with both clinical and laboratoryparameters. There is a need for novel biomarkers for prediction of severity in leptospirosis. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.Item Clinico-epidemiological characteristics, treatment and outcomes of patients with confirmed Leptospirosis in a Sri Lankan healthcare setting(Sri Lanka Medical Association, 2015) Rajapakse, S.; Weeratunga, P.N.; Rodrigo, C.; Sriharan, S.; Niloofa, M.J.R.; Fernando, N.; de Silva, H.J.; Karunanayake, L.; Premawansa, S.INTRODUCTION AND OBJECTIVES: Leptospirosis is a zoonotic infection caused by spirochaetes of the genus Leptospira, with humans being affected as incidental hosts. Leptospirosis is endemic in Sri Lanka. There is paucity of prospective data on the clinico-epidemiological characteristics, treatment profiles and outcomes of patients with ieptospirosis in Sri Lanka. METHOD: This was a prospective cross sectional study of patients, over 12 years of age, with a diagnosis of ieptospirosis based on the WHO surveillance criteria with subsequent laboratory confirmation, presenting to three hospitals in the Western province of Sri Lanka. RESULTS: Of a total of 178 patients, males (84.3%) between the ages of 40-49 years were more likely to be affected. 51.7% were direct admissions and 47.8% were transfers. Exposure to water potentially contaminated with rat urine was seen in the majority (71.9%). A significant proportion of patients developed acute kidney injury (66.9%). Penicillin was the most commonly used antibiotic for treatment (47.2%), however more than one antibiotic was used in 43.3%. The use of chemoprophylaxis by the patients was low (1.1%). Hemodialysis was needed for 36.5%. Recovery was seen in 71.3%, 2.8% died, 10.1% were transferred out and 15.8% were lost to follow-up. On discharge, 70.6% had been treated for severe leptospirosis. Mean length of hospital stay was 7.5 days (±5.1). CONCLUSION: The incidence of severe leptospirosis with organ dysfunction is higher in patients presenting to hospitals in the .Western province. Males aged 40-49 are most commonly affected. More than two thirds of the patients developed acute kidney Injury. Chemoprophylaxis rates were low.Item Development of an in-house ELISA as an alternative method for the serodiagnosis of leptospirosis(Elsevier, 2021) Niloofa, R.; Karunanayake, L.; de Silva, H.J.; Premawansa, S.; Rajapakse, S.; Handunnetti, S.BACKGROUND: Leptospirosis is most often clinically diagnosed and a laboratory test with high diagnostic accuracies is required. METHODOLOGY: IgM and IgG-ELISAs using Leptospira antigens were established and evaluated in relation to the Microscopic Agglutination Test (MAT). Antigen preparation consisted either saprophytic Leptospira biflexa to detect genus specific antibodies (genus-specific ELISA) or a pool of five most prevalent Leptospira interrogans serovars in Sri Lanka to detect serovar specific antibodies (serovar-specific ELISA). IgM and IgG immune responses in severe and mild leptospirosis patients (n = 100 in each group) were studied. RESULTS: ELISAs showed high repeatability and reproducibility. Serovar-specific IgM-ELISA showed sensitivity of 80.2% and specificity of 89%; genus-specific IgM-ELISA showed sensitivity of 83.3% and specificity of 91%. Serovar and genus-specific IgG-ELISA showed sensitivities of 73.3% and 81.7%, and specificities of 83.33%. Commercial IgM-ELISA showed sensitivity and specificity of 79.2% and 93% respectively. Commercial IgG-ELISA showed sensitivity, specificity of 50% and 96.7% respectively. IgM levels observed in mild and severe leptospirosis (ML & SL) patients were significantly higher than healthy control (HC) group, having absorbance mean of 0.770, 0.778 and 0.163 respectively. In contrast, SL patients had significantly higher mean anti-leptospiral IgG levels compared to both ML and HC groups (0.643, 0.358 and 0.116 respectively; ANOVA, P < 0.001). Presence of anti-leptospiral IgG above OD 0.643 optical density (OD) at 1:100 could predict high risk of severe disease. CONCLUSION: Serovar-specific In-House ELISAs could be used for the laboratory diagnosis of leptospirosis in endemic settings. Observed high levels of anti-leptospiral IgG suggest its value as a predictor for disease severity. KEYWORDS: IgM and IgG antibodies; In-House ELISA; Leptospirosis; Sero-diagnosis.Item Development of Suitable Propagation Systems for Tephrosia spp. in Sri Lanka(University of Kelaniya, 2014) Priyadarshan, A.I.S.; Senanayake, S.P.; Jayatilleke, M.P.; Rajapakse, S.Genus Tephrosia (Fabaceae) commonly known as ‘Pila’ in Sri Lanka. Some Tephrosia spp. are used in many traditional therapeutic preparations in Sri Lanka and also in other countries. Increased use of Tephrosia in traditional therapeutic systems has developed a great demand for these species. Thus production of planting materials for commercial cultivation has become a timely requirement. Therefore, this research was conducted to determine suitable propagation systems for four selected Tephrosia spp.; T. purpurea, T. villosa, T. noctiflora and T. pumila. Even though seeds of Tephrosia spp. showed high viability, lower germination percentage was observed on wet filter paper as well as in six different potting media [M0 (Coir: dust: Sand; 1:1:1), M1 (Coir dust: Sand: Top soil; 1:1:1), M2 (Coir dust: Sand: Top soil: Compost; 1:1:1:1), M3 (Coir dust: Sand: Top soil: Compost: Cow dung; 1:1:1:1:1), M4 (Coir dust: Sand: Compost; 1:1:1), M5 (Coir dust: Sand: Top soil: Cow dung; 1:1:1:1)] during a period of one week. Water impermeability of seed coats was identified as the main reason for the seed dormancy in Tephrosia spp. and soaking seeds in Con. H2SO4: H2O; 3:1 for 25 minutes and rubbing seeds on sandpaper for 2 minutes were determined as suitable dormancy breaking methods. Variation was observed in the growth performance of Tephrosia spp. in six different potting media. Growth performances of seedlings of Tephrosia spp. in hydroponic solution and soil medium were observed and soil medium was selected as the most suitable medium for the growth of Tephrosia species based on their growth performances.Item Diagnosis of leptospirosis: comparison between microscopic agglutination test, IgM-ELISA and IgM rapid immunochromatography test(Public Library of Science, 2015) Niloofa, R.; Fernando, N.; de Silva, N.L.; Karunanayake, L.; Wickramasinghe, H.; Dikmadugoda, N.; Premawansa, G.; Wickremasinghe, A.R.; de Silva, H.J.; Premawansa, S.; Rajapakse, S.; Handunnetti, S.BACKGROUND: Leptospirosis is diagnosed on clinical grounds, and confirmed by microscopic agglutination test (MAT). IgM-ELISA (Serion-Virion) and immunochromatography test (Leptocheck-WB) are two immunodiagnostic assays for leptospirosis. Their sensitivity, specificity and applicability in Sri Lanka have not been systematically evaluated. METHODS: Clinically diagnosed leptospirosis patients (n = 919) were recruited from three hospitals in the Western Province of Sri Lanka, during June 2012 to December 2013. MAT, IgM-ELISA and Leptocheck-WB were performed on all patient sera. MAT titer of ≥400 in single sample, four-fold rise or seroconversion ≥100 in paired samples were considered as positive for MAT. For diagnostic confirmation, MAT was performed during both acute and convalescent phases. Anti-leptospiral IgM ≥20 IU/ml and appearance of a band in the test window were considered as positive for IgM-ELISA and Leptocheck-WB test respectively. Patients with an alternative diagnosis (n = 31) were excluded. Data analysis was performed using two methods, i) considering MAT as reference standard and ii) using Bayesian latent class model analysis (BLCM) which considers each test as imperfect. RESULTS: MAT, IgM-ELISA and Leptocheck-WB positivity were 39.8%, 45.8% and 38.7% respectively during the acute phase. Acute-phase MAT had specificity and sensitivity of 95.7% and 55.3% respectively, when compared to overall MAT positivity. IgM-ELISA and Leptocheck-WB had similar diagnostic sensitivity when compared with acute-phase MAT as the gold standard, although IgM-ELISA showed higher specificity (84.5%) than Leptocheck-WB (73.3%). BLCM analysis showed that IgM-ELISA and Leptocheck-WB had similar sensitivities (86.0% and 87.4%), while acute-phase MAT had the lowest sensitivity (77.4%). However, acute-phase MAT had high specificity (97.6%), while IgM-ELISA and Leptocheck-WB showed similar but lower specificity (84.5% and 82.9%). CONCLUSIONS: Both IgM-ELISA and Leptocheck-WB shows similar sensitivities and specificities. IgM-ELISA may be superior to MAT during the acute phase and suitable for early diagnosis of leptospirosis. Leptocheck-WB is suitable as a rapid immunodiagnostic screening test for resource limited settings.Item A diagnostic model for Leptospirosis for use in resource limited settings(Sri Lanka Medical Association, 2015) Rajapakse, S.; Weeratunga, P.N.; Rodrigo, C.; Sriharan, S.; Niloofa, M.J.R.; Fernando, N.; de Silva, H.J.; Karunanayake, L.; Premawansa, S.INTRODUCTION AND OBJECTIVES: Leptospirosis is a zoonotic infection with significant morbidity and mortality. In this prospective study, we attempted to develop a model for diagnosis of leptospirosis. METHOD: Data was extracted from a prospective multicentre study. All patients with a suspected diagnosis of leptospirosis based on the WHO surveillance criteria were recruited. A derivation cohort and a validation cohort were selected. Positive MAT was used as the gold standard and significant associations in the derivation cohort were selected for construction of a multivariate regression model. Adjusted odds ratios were extracted for significant variables. ROC curves were generated. RESULTS: A total of 592 patients were included with 450 (180 confirmed leptospirosis) in the derivation cohort and 142 (52 confirmed leptospirosis) in the validation cohort. The variables in the final model were: history of exposure to possible source of leptospirosis (OR=2.878;95% Cl=1.527-5.425;p=0.001), serum creatinine>150u.mol/L (OR =2.742; 95% CN1.474-5.101; p=0.001), neutrophil differential percentage (on day 3 of illness) > 82.8% of total WBC count (OR 2.063; 95% Cl = 1.109 - 3.837; p =0.022), serum bilirubin > 27 U/L (OR = 1.767;95%CI 0.968 - 3.226; p=0.050) and platelet count (on day 3 of illness)< 85,000/mm3 (OR=2.350; 95%CI=1.281 -4.313;p=0.006). The Nagelkerke R2 was 0.654. ROC analysis demonstrated a diagnostic model score >14 to have a sensitivity of 80% and a specificity of 60% in the diagnosis of leptospirosis against MAT as the gold standard. CONCLUSION: This proposed diagnostic model for diagnosis of leptospirosis is of potential value to clinicians treating acute febrile illness in areas with limited diagnostic facilities.Item A Diagnostic scoring model for Leptospirosis in resource limited settings(Public Library of Science, 2016) Rajapakse, S.; Weeratunga, P.; Niloofa, R.; Fernando, N.; de Silva, N.L.; Rodrigo, C.; Maduranga, S.; Nandasiri, N.; Premawansa, S.; Karunanayake, L.; de Silva, H.J.; Handunnetti, S.Leptospirosis is a zoonotic infection with significant morbidity and mortality. The clinical presentation of leptospirosis is known to mimic the clinical profile of other prevalent tropical fevers. Laboratory confirmation of leptospirosis is based on the reference standard microscopic agglutination test (MAT), direct demonstration of the organism, and isolation by culture and DNA detection by polymerase chain reaction (PCR) amplification. However these methods of confirmation are not widely available in resource limited settings where the infection is prevalent, and reliance is placed on clinical features for provisional diagnosis. In this prospective study, we attempted to develop a model for diagnosis of leptospirosis, based on clinical features and standard laboratory test results. METHODS: The diagnostic score was developed based on data from a prospective multicentre study in two hospitals in the Western Province of Sri Lanka. All patients presenting to these hospitals with a suspected diagnosis of leptospirosis, based on the WHO surveillance criteria, were recruited. Confirmed disease was defined as positive genus specific MAT (Leptospira biflexa). A derivation cohort and a validation cohort were randomly selected from available data. Clinical and laboratory manifestations associated with confirmed leptospirosis in the derivation cohort were selected for construction of a multivariate regression model with correlation matrices, and adjusted odds ratios were extracted for significant variables. The odds ratios thus derived were subsequently utilized in the criteria model, and sensitivity and specificity examined with ROC curves. RESULTS: A total of 592 patients were included in the final analysis with 450 (180 confirmed leptospirosis) in the derivation cohort and 142 (52 confirmed leptospirosis) in the validation cohort. The variables in the final model were: history of exposure to a possible source of leptospirosis(adjusted OR = 2.827; 95% CI = 1.517-5.435; p = 0.001) serum creatinine > 150 micromol/l (adjusted OR = 2.735; 95% CI = 1.374-4.901; p = 0.001), neutrophil differential percentage > 80.0% of total white blood cell count (adjusted OR 2.163; 95% CI = 1.309-3.847; p = 0.032), serum bilirubin > 30 micromol/l (adjusted OR = 1.717; 95% CI 0.938-3.456; p = 0.049) and platelet count < 85,000/mm3 (adjusted OR = 2.350; 95% CI = 1.481-4.513; p = 0.006). Hosmer-Lemeshow test for goodness of fit was 0.931. The Nagelkerke R2 was 0.622. The area under the curve (AUC) was noted as 0.762. A score value of 14 reflected a sensitivity of 0.803, specificity of 0.602, a PPV of 0.54, NPV of 0.84, a positive LR of 2.01 and a negative LR of 0.32. CONCLUSIONS: The above diagnostic model for diagnosis of leptospirosis is suggested for use in clinical settings. It should be further validated in clinical practice.Item Effect of antimicrobial agents on inflammatory cytokines in acute Leptospirosis(American Society for Microbiology, 2018) Fernando, N.; de Silva, R.; Hadunnetti, S.M.; Karunanayake, L.; de Silva, N.L.; de Silva, H.J.; Rajapakse, S.; Premawansa, S.The aim of this study was to assess the inflammatory cytokine response and possible association with antimicrobial treatment with penicillin, ceftriaxone, and doxycycline in acute leptospirosis. In the early acute stage, interleukin-10 (IL-10) levels were higher in mild cases than in severe cases (P = 0.01). IL-6 and IL-8 levels were low in patients who received >5 antimicrobial doses (P < 0.01). IL-8 levels were negatively correlated with the number of ceftriaxone doses administered (r = -0.315; P = 0.031). Further studies are needed to evaluate the possible downregulation of proinflammatory cytokines by ceftriaxone in leptospirosis.Item Evaluation of the effect of oxidizing and reducing agents on trypsin inhibitory activity of Vigna mungo seeds (Black Gram)(Faculty of Science, University of Kelaniya, Sri Lanka, 2021) Jayasinghe, J. D. M. S.; Chandrasena, U. S. D.; Kumari, K. D. K. P.; Rajapakse, S.; Suresh, T. S.Trypsin is one of the widely distributed serine proteases in living organisms, which is involved in vital physiological functions. In spite of its involvement in survival of the organisms, it was reported that trypsin is associated in pathogenesis of different type of human cancers. Therefore, trypsin inhibitory proteins have been gained attention as a potential treatment strategy against such cancers. Seeds of legumes have been recognized as potential natural resources of trypsin inhibitory proteins. Black gram (Vigna mungo) is a popular legume cultivated in Sri Lanka and Field Crops Research and Development Institute of Sri Lanka (FCRDI) has released a novel breed of black gram called Anuradha. The attempts were made to assess trypsin inhibitory activity (TIA) of its seeds and characterization of the active trypsin inhibitory proteins for future discovery of anticancer agents. The objectives of the present study was to evaluate the effect of oxidizing and reducing agents on the activity of trypsin inhibitory proteins present in seed of the local variety and to investigate the ionic nature of active proteins using ion exchange chromatography. Fresh mature seeds of variety Anuradha were collected from FCRDI and the crude protein extract (20%) of milled seeds was prepared using distilled water. The TIA of the extract was assessed by the method explained by Kunitz (1947) with slight modifications. To evaluate the effect of oxidizing and reducing agents on TIA, the seed extract was incubated with hydrogen peroxide (1-2%, v/v), dimethyl sulphoxide (1-5%, v/v) and varying concentrations of β-mercaptoethanol for 30 minutes, followed by the measurement of TIA. To discover the ionic nature of the active proteins, the crude protein extract was fractionated by ion exchange chromatography using positively charged Diethylaminoethyl cellulose as the stationary phase. The column was washed with phosphate buffer (pH 7.4) and then eluted with 1 M NaCl. The absorbance of each eluted fraction was measured at 280 nm. The TIA was assessed for the fractions with highest absorbance values. The TIA activity of the crude protein extract was 73.21 ± 0.29%. In the presence of the oxidizing agents, dimethyl sulfoxide and hydrogen peroxide the TIA of the test extract was 59.91 ± 0.69% and 27.08 ± 0.34% respectively. The activity of seed samples incubated with 0.1 M, 0.5 M, 1 M and 2 M of β-mercaptoethanol was 70.72 ± 0.23%, 58.63 ± 0.53%, 46.31 ± 0.72% and 39.47 ± 0.44% respectively. Ion exchange chromatography resulted one fraction with high protein content at pH 7.4 which exhibited 3.12 ± 0.62% of TIA. The TIA of the washing fraction was 35.46 ± 0.08%. The results of the present study revealed that Dimethyl sulfoxide decreased the TIA in a moderate level while hydrogen peroxide caused a drastic decrease. Increasing concentration of the reducing agent β- mercaptoethanol gradually decreased the TIA of the test sample. The observations of column chromatography indicated that the seed sample of black gram contain active trypsin inhibitory proteins which exist in an anionic or neutral form in pH 7.4.Item Evaluation of two immunodiagnostic tests for early rapid diagnosis of leptospirosis in Sri Lanka: a preliminary study(BioMed Central, 2015) Eugene, E.J.; Handunnetti, S.M.; Wickramasinghe, S.A.; Kalugalage, T.L.; Rodrigo, C.; Wickremesinghe, H.; Dikmadugoda, N.; Somaratne, P.; de Silva, H.J.; Rajapakse, S.BACKGROUND: Leptospirosis is often treated based on clinical diagnosis. There is a need for rapid laboratory diagnosis for this condition. The aim of this study was to compare the diagnostic accuracy of two rapid IgM based immunodiagnostic assays with the microscopic agglutination test (MAT), in acute leptospirosis infection. METHODS: MAT, IgM based immunochromatographic test (Leptocheck-WB) and IgM ELISA were performed using acute sera of patients clinically suspected to have leptospirosis (n = 83). Bayesian latent class modeling was used to compare the accuracy of these tests. RESULTS: Percentage positivity for MAT, Leptocheck-WB, and IgM ELISA were 48.1, 55.3, and 45.7 % respectively. Bayesian latent class modeling showed a combined positivity rate of leptospirosis of 44.7 %. The sensitivity of MAT, Leptocheck-WB and IgM ELISA were 91.4, 95 and 81.1 %, and specificity were 86.7, 76.4 and 83.1 %, respectively. CONCLUSIONS: Leptocheck-WB has high sensitivity, and, because it is quick and easy to perform, would be a good screening test for acute leptospirosis infection. IgM ELISA has good specificity, and is comparable with MAT; given that it is easier to perform and more widely available than MAT, it would be a more appropriate confirmatory test for use in hospitals with limited access to a specialized laboratory.Item Extensive systemic thrombo-embolism including intra-cardiac thrombosis mimicking an atrial myxoma in a patient with beta thalassaemia major - a case report(BioMed Central, 2023) Welhenge, C.; Ranasinghe, R.; Rajapakse, S.; Premawardhena, A.BACKGROUND: Sepsis and thrombo-embolic disease are well known complications of thalassemia major. Intracardiac thrombi are however rare and can lead to diagnostic dilemmas. CASE PRESENTATION: We report the case of a 20-year-old female splenectomised thalassaemia major patient with severe iron overload, who presented with life threatening sepsis associated with a liver abscess. Discovery of a large oscillating intra cardiac lesion on 2D echocardiogram confrmed by Contrast Enhanced Computed Tomography (CECT) chest in the right atrium extending from the left hepatic vein through the inferior vena cava complicated the clinical course. After a prolonged Intensive Care Unit (ICU) stay supported with antibiotics and anticoagulation, she recovered with evidence of resolution of the intra cardiac thrombus. CONCLUSIONS: Early recognition and prompt aggressive treatment of sepsis in patients with thalassemia is essential to prevent complications. Intracardiac thrombosis is a potentially treatable cause for an intra cardiac mass in patients with thalassemia major, which should not be missed.Item First co-infection of malaria and hepatitis E diagnosed in Sri Lanka(Sri Lanka Medical Association, 2023) Senarathne, S.; Rajapakse, S.; de Silva, H.J.; Seneviratne, S.; Chulasiri, P.; Fernando, D.INTRODUCTION: Imported malaria cases continue to be reported in Sri Lanka. Similarly, hepatitis E is also considered a travel associated imported disease in Sri Lanka. This is a report of the first co-infection of malaria and hepatitis E in Sri Lanka. OBJECTIVES: A 21-year-old European who visited Sri Lanka after a 2 months stay in India, was admitted to hospital with fever, vomiting, abdominal pain, and dark-coloured urine on the 4th day after his arrival. On examination, he had splenomegaly but no hepatomegaly. He had thrombocytopaenia; 89% neutrophils; 9% lymphocytes; elevated liver enzymes and hyperbilirubinaemia. Urine was positive for bile pigment. METHODS: Considering his travel history to India, he was tested for malaria. The rapid diagnostic test became positive for Plasmodium falciparum while microscopy showed P. falciparum ring stages with a parasite density of 120/μl. He was treated as for uncomplicated P. falciparum malaria with oral Artemisinin-based Combination Therapy. The patient became fever-free and blood smears became negative after 13 hours following 2 doses of antimalarials. RESULTS: However, his liver functions were further deranged with apparent jaundice (ALT: 250 U/L; AST: 175 U/L; ALP: 130 U/L; GGT: 179 U/L; total bilirubin: 10.65 mg/dL; direct bilirubin: 8.08 mg/dL; indirect bilirubin: 2.57 mg/dL). Further blood tests detected hepatitis E-specific IgM antibodies. He was treated with oral ursodiol but no specific antiviral was given. Following the completion of antimalarials, he was discharged from the hospital upon clinical recovery. CONCLUSION: Clinicians should be vigilant on travel-associated co-infections in patients who are diagnosed with imported malaria.Item The first reported case of co-infection of imported hepatitis E and Plasmodium falciparum malaria in Sri Lanka(Sri Lankan Society for Microbiology, 2023) Senarathne, S.; Rajapakse, S.; de Silva, H.J.; Seneviratne, S.; Chulasiri, P.; Fernando, D.Global travel and tourism, especially across tropical countries, may lead to importation of malaria and other infectious diseases into Sri Lanka. This case report describes the first co-infection of imported hepatitis E and Plasmodium falciparum malaria in a tourist diagnosed in Sri Lanka. The patient was initially diagnosed with uncomplicated P. falciparum malaria and was started on treatment with oral Artemisinin-based Combination Therapy (ACT). Deterioration of hepatic enzymes and hyperbilirubinaemia despite the rapid parasitological response to antimalarials led to further investigation and diagnosis of co-infecting hepatitis E in this patient. The importance of clinicians being vigilant on travel associated co-infections is highlighted to ensure early diagnosis and better patient management.Item Fixed low-dose triple combination Antihypertensive Medication vs usual care for blood pressure control in patients with mild to moderate hypertension in Sri Lanka: A Randomized Clinical Trial(American Medical Association, 2018) Webster, R.; Salam, A.; de Silva, H.A.; Selak, V.; Stepien, S.; Rajapakse, S.; Amarasekara, N.; Amarasena, N.; Billotm, L.; de Silva, A.P.; Fernando, M.; Guggilla, R.; Jan, S.; Jayawardena, J.; Maulik, P.K.; Mendis, S.; Mendis, S.; Munasinghe, J.; Naik, N.; Prabhakaran, D.; Ranasinghe, G.; Thom, S.; Thisserra, N.; Senaratne, V.; Wijekoon, S.; Wijeyasingham, S.; Rodgers, A.; Patel, A.; TRIUMPH Study GroupIMPORTANCE: Poorly controlled hypertension is a leading global public health problem requiring new treatment strategies. OBJECTIVE: To assess whether a low-dose triple combination antihypertensive medication would achieve better blood pressure (BP) control vs usual care. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label trial of a low-dose triple BP therapy vs usual care for adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg; or in patients with diabetes or chronic kidney disease: >130 mm Hg and/or >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. INTERVENTIONS: A once-daily fixed-dose triple combination pill (20 mg of telmisartan, 2.5 mg of amlodipine, and 12.5 mg of chlorthalidone) therapy (n = 349) or usual care (n = 351). MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion achieving target systolic/diastolic BP (<140/90 mm Hg or <130/80 mm Hg in patients with diabetes or chronic kidney disease) at 6 months. Secondary outcomes included mean systolic/diastolic BP difference during follow-up and withdrawal of BP medications due to an adverse event. RESULTS: Among 700 randomized patients (mean age, 56 years; 58% women; 29% had diabetes; mean baseline systolic/diastolic BP, 154/90 mm Hg), 675 (96%) completed the trial. The triple combination pill increased the proportion achieving target BP vs usual care at 6 months (70% vs 55%, respectively; risk difference, 12.7% [95% CI, 3.2% to 22.0%]; P < .001). Mean systolic/diastolic BP at 6 months was 125/76 mm Hg for the triple combination pill vs 134/81 mm Hg for usual care (adjusted difference in postrandomization BP over the entire follow-up: systolic BP, -9.8 [95% CI, -7.9 to -11.6] mm Hg; diastolic BP, -5.0 [95% CI, -3.9 to -6.1] mm Hg; P < .001 for both comparisons). Overall, 419 adverse events were reported in 255 patients (38.1% for triple combination pill vs 34.8% for usual care) with the most common being musculoskeletal pain (6.0% and 8.0%, respectively) and dizziness, presyncope, or syncope (5.2% and 2.8%). There were no significant between-group differences in the proportion of patient withdrawal from BP-lowering therapy due to adverse events (6.6% for triple combination pill vs 6.8% for usual care). CONCLUSIONS AND RELEVANCE: Among patients with mild to moderate hypertension, treatment with a pill containing low doses of 3 antihypertensive drugs led to an increased proportion of patients achieving their target BP goal vs usual care. Use of such medication as initial therapy or to replace monotherapy may be an effective way to improve BP control.Item Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial.(The Lancet. Global health., 2019) Lung, T.; Jan, S.; de Silva, H.A.; Guggilla, R.; Maulik, P.K.; Naik, N.; Patel, A.; de Silva, A.P.; Rajapakse, S.; Ranasinghe, G.; Prabhakaran, D.; Rodgers, A.; Salam, A.; Selak, V.; Stepien, S.; Thom, S.; Webster, R.; Lea-Laba, T.; TRIUMPH Study Group.BACKGROUND: Elevated blood pressure incurs a major health and economic burden, particularly in low-income and middle-income countries. The Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial showed a greater reduction in blood pressure in patients using fixed-combination, low-dose, triple-pill antihypertensive therapy (consisting of amlodipine, telmisartan, and chlorthalidone) than in those receiving usual care in Sri Lanka. We aimed to assess the cost-effectiveness of the triple-pill strategy. METHODS: We did a within-trial (6-month) and modelled (10-year) economic evaluation of the TRIUMPH trial, using the health system perspective. Health-care costs, reported in 2017 US dollars, were determined from trial records and published literature. A discrete-time simulation model was developed, extrapolating trial findings of reduced systolic blood pressure to 10-year health-care costs, cardiovascular disease events, and mortality. The primary outcomes were the proportion of people reaching blood pressure targets (at 6 months from baseline) and disability-adjusted life-years (DALYs) averted (at 10 years from baseline). Incremental cost-effectiveness ratios were calculated to estimate the cost per additional participant achieving target blood pressure at 6 months and cost per DALY averted over 10 years. FINDINGS: The triple-pill strategy, compared with usual care, cost an additional US$9·63 (95% CI 5·29 to 13·97) per person in the within-trial analysis and $347·75 (285·55 to 412·54) per person in the modelled analysis. Incremental cost-effectiveness ratios were estimated at $7·93 (95% CI 6·59 to 11·84) per participant reaching blood pressure targets at 6 months and $2842·79 (-28·67 to 5714·24) per DALY averted over a 10-year period. INTERPRETATION: Compared with usual care, the triple-pill strategy is cost-effective for patients with mild-to-moderate hypertension. Scaled up investment in the triple pill for hypertension management in Sri Lanka should be supported to address the high population burden of cardiovascular disease.Item Host Plant Preference of Genera Dendrobium and Bulbophyllum (Family: Orchidaceae) in Sri Lanka.(International Research Symposium on Pure and Applied Sciences, 2017 Faculty of Science, University of Kelaniya, Sri Lanka., 2017) Sandamali, P. M. H.; Senanayake, S. P.; Benjamin, S. P.; Rajapakse, S.; Athukorala, N. P.Orchids are a well-known plant family for their restricted distribution in the wild. Most epiphytic orchids are hosted by specific trees and hence it’s abundance may be influenced by the availability of suitable host trees and epiphytic composition. The distribution of many epiphytic orchids in nature indicates that they display strong species specificity in selecting hosts and noticeably lacking on other trees. Dendrobium and Bulbophyllum are epiphytic genera and mostly have restricted distribution in the natural environments. Furthermore; they display a biased distribution towards host trees. Therefore, the study aims to investigate the host tree preference of the species of Dendrobium and Bulbophyllum with a view to provide important information for the conservation of these species. Wet forests in Matale (Knuckles mountain range), Nuwara Eliya (Hakgala nature reserve, Horton Plains National Park, Pidurutalagala mountain, Kandeela forest reserve), Baddulla (Namunukula mountain), Kegalle (Makandawa forest reserve), Ratnapura (Sinharaja rain forest, Peak wilderness), Kurunegala (Kankaniyammulla forest), Galle (Hiyare rain forest, Kottawa forest, Morningside forest) districts were explored for the distribution of two genera; Dendrobium and Bulbophyllum. Specimens were collected randomly from the selected sites; three plots of 500m× 500m size per each site, and relevant data of host plants were recorded such as tree height, girth at breast height (GBH), tree bark characteristics (bark colour, nature of the moss cover and bark texture) and the abundance of orchid species on the host tree. Further, herbarium specimens of host trees and the orchids were prepared for identification. Presence of orchid species on the identified host trees was counted and, percentage of frequency was calculated. It was revealed that the orchids are mostly associated with hosts with dense moss cover and rough tree barks. Sixty five percent of species of Dendrobium and Bulbophyllum were found on hosts having 51-100 cm GBHs. Further, these orchids have shown preference to plant families; Myrtaceae (26%), Lauraceae (23%) and Phylanthaceae (16%) as their hosts, whereas, with respect to the genus specificity, highest percentage of these orchids have shown preference to genera Syzygium (family Myrtaceae) and Glochidion (family Phylanthaceae) as their hosts. Findings of the present study have revealed that the species diversity and species richness of genera Dendrobium and Bulbophyllum were high in the montane forests located in Nuwara Eliya (Horton Plains Nature Park, Kandeela forest reserve and Pidurutalagala mountain) and Matale (Knuckles mountain range) districts. This might be due to the fact that these forests were characterized by high humidity and high elevation. Chemical composition, distribution of moss cover and fungi associated with tree barks of these preferred host trees, would provide new insight for the conservation of these epiphytic orchid species.