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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 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 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 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 Low serum total nitrite and nitrate levels in severe leptospirosis(BioMed Central, 2013) Kalugalage, T.; Rodrigo, C.; Vithanage, T.; Somaratne, P.; de Silva, H.J.; Handunnetti, S.; Rajapakse, S.BACKGROUND: The relationship between inducible nitric oxide synthatase activity and disease severity in leptospirosis is unclear. Nitric oxide is converted to nitrites and nitrates, thus nitrite and nitrate levels (NOx) in serum are considered surrogate markers for nitric oxide. NOx are excreted through the kidneys, and elimination is diminished in renal impairment. We assessed the correlation of NOx with disease severity in patients with leptospirosis, compared with healthy controls and non-leptospirosis fever patients. METHODS: All patients admitted over a two-month period to the National Hospital, Colombo, Sri Lanka with a clinical picture suggestive ofleptospirosis were included. Leptospirosis was confirmed by the microscopic agglutination test (titre ≥ 400). Severe leptospirosis was defined by the presence of two or more of the following criteria: jaundice (bilirubin> 51.3 μmol/l), oliguria (urine output < 400 ml/day), serum creatinine> 133 μmol/l or blood urea > 25.5 mmol/l, or the presence of organ dysfunction. Non-leptospirosis fever patients and healthy volunteers were used as control groups. NOx levels were measured using a modified Griess reaction. RESULTS: Forty patients were confirmed as having leptospirosis and 26 of them had severe disease. NOx levels were significantly higher in confirmed leptospirosis patients compared to healthy controls, MAT equivocal patients and non-leptospirosis fever patients (p<0.001). NOx concentrations were also significantly higher in patients with severe compared to mild leptospirosis (p<0.001). Once NOx levels were corrected for renal function, by using the ratio NOx/creatinine, NOx levels were actually significantly lower in patients with severe disease compared to other patients, and values were similar to those of healthy controls. CONCLUSIONS: We postulate that high NOx levels may be protective against severe leptospirosis, and that finding low NOx levels (when corrected for renal function) in patients with leptospirosis may predict the development of severe disease and organ dysfunction. © 2013 Kalugalage et al.; licensee BioMed Central Ltd.