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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Effectiveness of passive case detection for imported malaria in a hospital setting in Sri Lanka during the prevention of re-introduction phase of malaria(Oxford University Press, 2019) Dharmawardena, P.; Premaratna, R.; Mendis, K.; Wickremasinghe, A.R.; Rodrigo, C.; Harintheran, A.; Fernando, D.INTRODUCTION: The effectiveness of the passive case detection (PCD) system for imported malaria was assessed in government hospitals in Sri Lanka post-elimination of malaria. METHODS: In 18 medical wards (test wards) in four government hospitals, the referral for malaria testing and the diagnosis of malaria by the ward physicians were monitored. Concurrently, in-ward febrile patients were assessed independently for their eligibility for referral for malaria diagnosis and were tested for malaria. The malaria incidence in 16 other wards (control wards), which the study did not screen, served as controls. RESULTS: Four imported malaria patients were diagnosed within the PCD system among 25 874 febrile patients admitted during the 14-month study period, two of whom were diagnosed in the test wards and two in the control wards. The study's screening programme did not detect any more malaria patients than detected by the routine PCD system of the wards. However, far fewer patients were screened for malaria (1.3%) than were eligible for screening (29.4%), and some infections were detected incidentally, rather than by a request for a malaria test. CONCLUSION: A continuous effort to maintain awareness of the disease among physicians would be required if the PCD system is to be effective for the detection of imported malaria, post-elimination.Item Use of a public-private partnership in malaria elimination efforts in Sri Lanka; a case study(BioMed Central, 2018) Fernando, D.; Wijeyaratne, P.; Wickremasinghe, R.; Abeyasinghe, R.R.; Galappaththy, G.N.L.; Wickremasinghe, R.; Hapugoda, M.; Abeyewickreme, W.; Rodrigo, C.BACKGROUND: In special circumstances, establishing public private partnerships for malaria elimination may achieve targets faster than the state sector acting by itself. Following the end of the separatist war in Sri Lanka in 2009, the Anti Malaria Campaign (AMC) of Sri Lanka intensified malaria surveillance jointly with a private sector partner, Tropical and Environmental Diseases and Health Associates Private Limited (TEDHA) with a view to achieving malaria elimination targets by 2014. METHODS: This is a case study on how public private partnerships can be effectively utilized to achieve malaria elimination goals. TEDHA established 50 Malaria Diagnostic Laboratories and 17 entomology surveillance sentinel sites in consultation with the AMC in areas difficult to access by government officials (five districts in two provinces affected by war). RESULTS: TEDHA screened 994,448 individuals for malaria, of which 243,867 were screened at mobile malaria clinics as compared to 1,102,054 screened by the AMC. Nine malaria positives were diagnosed by TEDHA, while the AMC diagnosed 103 malaria cases in the same districts in parallel. Over 13,000 entomological activity days were completed. Relevant information was shared with AMC and the data recorded in the health information system. CONCLUSIONS: A successful public-private partnership model for malaria elimination was initiated at a time when the health system was in disarray in war ravaged areas of Sri Lanka. This ensured a high annual blood examination rate and screening of vulnerable people in receptive areas. These were important for certification of malaria-free status which Sri Lanka eventually received in 2016.Item Contribution of the private sector healthcare service providers to malaria diagnosis in a prevention of re-introduction setting(BioMed Central, 2016) Fernando, S.D.; Dharmawardena, P.; Epasinghe, G.; Senanayake, N.; Rodrigo, C.; Premaratna, R.; Wickremasinghe, R.BACKGROUND: Sri Lanka is currently in the prevention of re-introduction phase of malaria. The engagement of the private sector health care institutions in malaria surveillance is important. The purpose of the study was to determine the number of diagnostic tests carried out, the number of positive cases identified and the referral system for diagnosis in the private sector and to estimate the costs involved. METHODS: This prospective study of private sector laboratories within the Colombo District of Sri Lanka was carried out over a 6-month period in 2015. The management of registered private sector laboratories was contacted individually and the purpose of the study was explained. A reporting format was developed and introduced for monthly reporting. RESULTS: Forty-one laboratories were eligible to be included in the study and 28 participated by reporting data on a monthly basis. Excluding blood bank samples and routine testing for foreign employment, malaria diagnostic tests were carried out on 973 individuals during the 6-month period and nine malaria cases were identified. In 2015, a total of 36 malaria cases were reported from Sri Lanka. Of these, 24 (67 %) were diagnosed in the Colombo District and 50 % of them were diagnosed in private hospitals. CONCLUSIONS: An equal number of cases were diagnosed from the private sector and government sector in the Colombo District in 2015. The private sector being a major contributor in the detection of imported malaria cases in the country should be actively engaged in the national malaria surveillance system.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 Protein Carbonyl as a biomarker of oxidative stress in severe Leptospirosis, and its usefulness in differentiating Leptospirosis from Dengue Infections(Public Library of Science, 2016) Fernando, N.; Wickremesinghe, S.; Niloofa, R.; Rodrigo, C.; Karunanayake, L.; de Silva, H.J.; Wickremasinghe, A.R.; Premawansa, S.; Rajapakse, S.; Handunnetti, S.M.Pathogenesis of disease severity in leptospirosis is not clearly understood whether it is due to direct damage by pathogen or by adverse immune responses. Knowledge on biomarkers of oxidative stress which could be used in identifying patients with severe illness has shown to be of great value in disease management. Thus, the main aim of this study was to assess the damage to serum proteins and lipids, and their significance as biomarkers of oxidative stress in severe leptospirosis. In regions endemic for both leptospirosis and dengue, leptospirosis cases are often misdiagnosed as dengue during dengue epidemics. Therefore, the second aim was to assess the potential of the oxidative stress markers in differentiating severe leptospirosis from critical phase dengue. We measured serum antioxidants (uric acid and bilirubin), total antioxidant capacity (AOC), protein carbonyl (PC) and lipid hydroperoxide (LP) in patients with severe leptospirosis (n = 60), mild leptospirosis (n = 50), dengue during the critical phase (n = 30) and in healthy subjects (n = 30). All patient groups had similar total antioxidant capacity levels. However, the presence of significantly high uric acid and total bilirubin levels may reflect the degree of renal and hepatic involvement seen in severe leptospirosis patients (p<0.02). Serum PC and LP levels were significantly higher in leptospirosis patients compared to critical phase dengue infections (p<0.005). Moreover, high serum PC levels appear to differentiate SL from DC [area under the curve (AUC) = 0.96; p<0.001]. Serum PC may be a reliable biomarker of oxidative damage to serum proteins to identify severe leptospirosis patients (AUC = 0.99) and also to differentiate severe leptospirosis from mild cases (AUC = 0.78; p<0.005) indicating its contribution to pathogenesis. Use of serum PC as an indicator of leptospirosis severity and as an oxidative stress biomarker in differentiating leptospirosis from dengue would provide the opportunity to save lives via prompt patient management.Item A pilot study on comparison of rapid immunodiagnostics for confirmation of leptospirosis(Sri Lanka Medical Association, 2012) Eugene, E.J.; Wickramasinghe, S.A.; Kalugalage, T.L.; Rodrigo, C.; Wickremesinghe, H.; Dikmadugoda, N.; Somaratne, P.; de Silva, H.J.; Rajapakse, S.; Handunnetti, S.M.INTRODUCTION: In Sri Lanka, leptospirosis is mostly diagnosed on clinical grounds. Serological confirmation is not obtainable during the acute stage of the illness. There is a need for rapid immunodiagnostics for confirmation of leptospirosis. Two immunodiagnostic assays, ie: enzyme linkedimmnnosorbent assay (ELISA) and immunochromatographic technique Leptocheck-WB test (LCT) areused to detect leptospira specific IgM antibodies which are prevalent in early stages of acute infections. AIMS: To compare the efficacy of these two rapid immunodiagnostic assays with the microscopic agglutination assay (MAT) to determine their applicability. Methods: A set of sera (n=83) collected in 2010 for which MAT titres were available was used to perform IgMELISAandLCT. RESULTS: Positivity for LCT and IgM ELISA were 55.4% and 48.2% respectively, and both assays detected acute infection by day 3 of the illness. MAT> 400 was used as the reference standard. For LCT, the overall sensitivity, specificity, accuracy, PPV and NPV (86.5%, 75.0%, 79.6%, 69.6% and 89.4% respectively) were higher compared to the respective values for IgM ELISA (50.0%, 62.3%, 57.1%, 50.0%, 62.3%). The highest of these values were observed during the first week for LCT and during the second week for IgM ELISA. The highest agreement was observed between LCT and MAT>400 (p=0.568) and there was a good agreement between LCT and IgM ELISA (p=0.520). CONCLUSIONS: The high sensitivity and specificity, ease of use, and non-requirement of specialized skills and equipment makes LCT a good choice for screening, while IgM ELISA is an appropriate test for confirming acute leptopsirosis.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 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 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. 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