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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Double-trouble: A rare case of co-infection with melioidosis and leptospirosis from Sri Lanka(Sage, 2023) Gunasena, J.B.; de Silva, S.T.Melioidosis and leptospirosis are two emerging tropical infections that share somewhat similar clinical manifestations but require different methods of management. A 59-year-old farmer presented to a tertiary care hospital with an acute febrile illness associated with arthralgia, myalgia and jaundice, complicated by oliguric acute kidney injury and pulmonary haemorrhage. Treatment was initiated for complicated leptospirosis but with poor response. Blood culture was positive for Burkholderia pseudomallei and microscopic agglutination test (MAT) for leptospirosis was positive at the highest titres of 1:2560, confirming a co-infection of leptospirosis and melioidosis. The patient made a complete recovery with therapeutic plasma exchange (TPE), intermittent haemodialysis and intravenous (IV) antibiotics. Similar environmental conditions harbour melioidosis and leptospirosis, making co-infection a very real possibility. Co-infection should be suspected in patients from endemic areas with water and soil exposure. Using two antibiotics to cover both pathogens effectively is prudent. IV penicillin with IV ceftazidime is one such effective combination.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 Application of a real time Polymerase Chain Reaction (PCR) assay for the early diagnosis of human leptospirosis in Sri Lanka(Academic Press, Elsevier, 2016) Denipitiya, D.T.H.; Chandrasekharan, N.V.; Abeyewickreme, W.; Hartskeerl, C.M.; Hartskeerl, R.A.; Jiffrey, A.M.; Hapugoda, M.D.Leptospirosis has a major impact on health in Sri Lanka but is probably grossly under-recognized due to difficulties in clinical diagnosis and lack of diagnostic laboratory services. The objective of this study was to establish and evaluate a SYBR Green-based real-time Polymerase Chain Reaction (rt-PCR) assay for early, rapid and definitive laboratory diagnosis of leptospirosis in Sri Lanka. The rt-PCR assay was established and analytical specificity and sensitivity were determined using reference DNA samples. Evaluation of the assay for diagnosis of clinical samples was performed using two panels of serum samples obtained from 111 clinically suspected adult patients. Patients were confirmed as leptospirosis (n = 65) and non-leptospirosis (n = 30) by the Patoc - MAT. Other 16 samples gave ambiguous results. The analytical sensitivity of the rt-PCR was approximately 60 genome copies and no cross-reactivity was observed with saprophytic Leptospira spp. and other pathogenic microorganisms. Based on confirmation with Patoc-MAT on paired samples this corresponds to a diagnostic sensitivity and specificity of 67.7% (44/65) and 90.0% (27/30), respectively. This study showed that rt-PCR has the potential to facilitate rapid and definitive diagnosis of leptospirosis during early phase of infection in Sri Lanka.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. 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 Evidence of leptospira and Hanta virus co-infections amongst patients hospitalised for leptospirosis-like illness(Sri Lanka College of Microbiologists, 2003) Sunil-Chandra, N.P.; Premaratna, R.; Somasiri, D.A.D.H.; de Silva, H.J.INTRODUCTION: Hantavirus infection and leptospirosis are zoonoses with similar epidemiology and disease forms. Both infections spread to humans from infected rodents. OBJECTIVES: To assess the frequency and clinical manifestations of hantavirus infection in patients hospitalised with leptospirosis-like illness. METHODS: Two groups of patients admitted with leptospirosis-like illness to the University Medical Unit, Ragama, were investigated for evidence of both hantavirus infection and leptospirosis. Demographic data were obtained prospectively from 39 patients (Group 1) (M:F=34:5, mean age 35 yrs) (1996-1997), and retrospectively from 35 patients (Group 2) (M:F=34:1, mean age 30 yrs) who had been admitted to the unit during the previous year (1995-1996). Paired sera from 31/39 patients in Group 1 were tested for IgM antibodies and a single serum sample from 24/35 patients in Group 2 was tested for IgG antibodies to Hantaan and Puumala serotypes of hantavirus using m-capture ELISA separately. The same panels of sera were also tested for the presence of anti-leptospiral IgM (in Group 1) and IgG (in Group 2) antibodies. RESULTS: In Group 1, 9/31 and 25/31 sera were positive for hantavirus and leptospira IgM antibodies respectively. 5/31 were negative for both antibodies. 8/9 hantavirus IgM positive sera were also positive for leptospira IgM antibodies indicating co-infection. 1/9 showed seroconversion to hantavirus only, and 17/31 showed seroconversion to leptospira only. Based on the reactivity of hantavirus IgM antibody positive sera against recombinant hantavirus neucleocapsid proteins by m-capture ELISA, 5/9 had Puumala-like and 2/9 had Hantaan-like predominant antigenic specificities. The other 2/9 showed specificity to Puumala only. In Group 2, 10/24 and 23/24 sera were positive for hantavirus and leptospira IgG antibodies respectively. 1/24 was negative for both. All 10 hantavirus IgG antibody positive sera were also positive for leptospira IgG antibodies. 7 of 10 had specificity to Puumala, 2 of 10 had predominantly Puumala and 1 had predominantly Hantaan antigen specificity. Male predominance, occupations related to agriculture and farming, and exposure to rodents were risk factors associated with leptospirosis-like illness. Anorexia, nausea, and myalgia were features common to all patients More patients with hantavirus infection or with or without leptospirosis than those with leptospira infections only had hepatic (78% Vs. 17%) and renal (56% Vs. 17%) involvement during the course of their illness. Conclusions: In our study, hantavirus infection or co-infection with leptospirosis occurred in about one third of patients with leptospirosis-like illness admitted to hospital. The majority had hepatic and renal involvement. Three hantavirus serotypes, Puumala, Puumala-like and Hantaan-like, were detected.Item Concomitant leptospirosis-hantavirus co-infection in acute patients hospitalized in Sri Lanka: implications for a potentially worldwide underestimated problem(Cambridge University Press, 2015) Sunil-Chandra, N.P.; Clement, J.; Maes, P.; de Silva, H.J.; Van Esbroeck, M.; Van Ranst, M.Two global (re-)emerging zoonoses, leptospirosis and hantavirus infections, are clinically indistinguishable. Thirty-one patients, hospitalized in Sri Lanka for acute severe leptospirosis, were after exclusion of other potentially involved pathogens, prospectively screened with IgM ELISA for both pathogens. Of these, nine (29·0%) were positive for leptospirosis only, one (3·2%) for hantavirus only, seven (22·5%) for both pathogens concomitantly, whereas 13 (41·9%) remained negative for both. Moreover, in a retrospective study of 23 former patients, serologically confirmed for past leptospirosis, six (26·0%) were also positive in two different IgG ELISA hantavirus formats. Surprisingly, European Puumala hantavirus (PUUV) results were constantly higher, although statistically not significantly different, than Asian Hantaan virus (HTNV), suggesting an unexplained cross-reaction, since PUUV is considered absent throughout Asia. Moreover, RT-PCR on all hantavirus IgM ELISA positives was negative. Concomitant leptospirosis-hantavirus infections are probably heavily underestimated worldwide, compromising epidemiological data, therapeutical decisions, and clinical outcome.Item Spatial and seasonal analysis of human leptospirosis in the District of Gampaha, Sri Lanka(University of Kelaniya, 2014) Denipitiya, D.T.H.; Abeyewickreme, W.; Hapugoda, M.D.; Chandrasekharan, N.V.Leptospirosis is a zoonostic infectious disease, caused by a pathogenic species of the genus Leptospira. In Sri Lanka, around 1500 human leptospirosis cases are reported annually. Typically, the risk of the disease is seasonal with a small spike occurs in March to May and a large spike occurs during October to December. Objective of this study was to analyze spatial and seasonal pattern of human leptospirosis in the District of Gampaha, Sri Lanka.