Journal/Magazine Articles
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This collection contains original research articles, review articles and case reports published in local and international peer reviewed journals by the staff members of the Faculty of Medicine
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Item Proteome profiling of cutaneous leishmaniasis lesions due to dermotropic Leishmania donovani in Sri Lanka(BioMed Central, 2024) Manamperi, N.H.; Edirisinghe, N.M.; Wijesinghe, H.; Pathiraja, L.; Pathirana, N.; Wanasinghe, V.S.; De Silva, C.G.; Abeyewickreme, W.; Karunaweera, N.D.BACKGROUND Characterization of the host response in cutaneous leishmaniasis (CL) through proteome profiling has gained limited insights into leishmaniasis research compared to that of the parasite. The primary objective of this study was to comprehensively analyze the proteomic profile of the skin lesions tissues in patients with CL, by mass spectrometry, and subsequent validation of these findings through immunohistochemical methods.METHODS Eight lesion specimens from leishmaniasis-confirmed patients and eight control skin biopsies were processed for proteomic profiling by mass spectrometry. Formalin-fixed paraffin-embedded lesion specimens from thirty patients and six control skin specimens were used for Immunohistochemistry (IHC) staining. Statistical analyses were carried out using SPSS software. The chi-square test was used to assess the association between the degree of staining for each marker and the clinical and pathological features.RESULTS Sixty-seven proteins exhibited significant differential expression between tissues of CL lesions and healthy controls (p < 0.01), representing numerous enriched biological processes within the lesion tissue, as evident by both the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. Among these, the integrated endoplasmic reticulum stress response (IERSR) emerges as a pathway characterized by the up-regulated proteins in CL tissues compared to healthy skin. Expression of endoplasmic reticulum (ER) stress sensors, inositol-requiring enzyme-1 (IRE1), protein kinase RNA-like ER kinase (PERK) and activating transcription factor 6 (ATF6) in lesion tissue was validated by immunohistochemistry.CONCLUSIONS In conclusion, proteomic profiling of skin lesions carried out as a discovery phase study revealed a multitude of probable immunological and pathological mechanisms operating in patients with CL in Sri Lanka, which needs to be further elaborated using more in-depth and targeted investigations. Further research exploring the intricate interplay between ER stress and CL pathophysiology may offer promising avenues for the development of novel diagnostic tools and therapeutic strategies in combating this disease.Item ELISA based evaluation of antibody response to Leishmania in a region endemic for cutaneous leishmaniasis(Oxford, 2022) Piyasiri, S.B.; Samaranayake, T.N.; Silva, H.; Manamperi, N.H.; Karunaweera, N.D.Aims: Leishmaniasis includes several clinical forms. While routine diagnosis of cutaneous leishmaniasis (CL) is by microscopy, an antibody response to CL has been reported in several recent studies. This study evaluated anti-leishmanial IgG antibody responses as a biomarker of active leishmaniasis and a measure of exposure to Leishmania. Methods and results: Sera from 50 untreated CL patients, 140 patients under treatment and 280 healthy individuals residing in endemic regions collected as part of an epidemiological survey, was analysed with an ELISA established in-house using receiver-operator-characteristic (ROC) curve at optimised cut-off value. The assay showed high performance as a diagnostic tool in identifying exposure in endemic individuals (sensitivity: 98%, specificity: 90.3%). All patients showed lower antibody levels over time since onset of lesion/s. Antibody levels were higher (p ˂ 0.01) and persisted for a longer period in untreated patients. In patients under treatment, the level of anti-IgG antibodies was negatively correlated with the total duration the patient had been on treatment. Conclusion: The anti-leishmanial IgG response in L. donovani induced CL is transient and is unlikely to confer protective immunity. Optimised serological assays may be useful in endemic settings for diagnosis and monitoring the treatment response in CL.Item Spatial epidemiologic trends and hotspots of leishmaniasis, Sri Lanka, 2001-2018(Centers for Disease Control and Prevention (CDC), 2020) Karunaweera, N.D.; Ginige, S.; Senanayake, S.; Silva, H.; Manamperi, N.; Samaranayake, N.; Siriwardana, Y.; Gamage, D.; Senerath, U.; Zhou, G.;ABSTRACT: Leishmaniasis, a neglected tropical disease, is on the decline in South Asia. However, cases of cutaneous leishmaniasis have risen in Sri Lanka since 2001, and the lack of in-depth research on its epidemiologic characteristics hampers control efforts. We analyzed data collected from patients with cutaneous leishmaniasis in Sri Lanka during 2001-2018 to study temporal and geographic trends and identify and monitor disease hotspots. We noted a progression in case rates, including a sharp rise in 2018, showing temporal expansion of disease-prevalent areas and 2 persistent hotspots. The northern hotspot shifted and shrank over time, but the southern hotspot progressively expanded and remained spatially static. In addition, we noted regional incidence differences for age and sex. We provide evidence of temporally progressive and spatially expanding incidence of leishmaniasis in Sri Lanka with distinct geographic patterns and disease hotspots, signaling an urgent need for effective disease control interventions. KEYWORDS: Asia; Indian subcontinent; Leishmania donovani; Sri Lanka; cutaneous leishmaniasis; dermatological pathologies; epidemiology; infectious diseases; leishmaniasis; parasites; protozoa; skin lesions; vector-borne infections.Item Spatiotemporal distribution of cutaneous leishmaniasis in Sri Lanka and future case burden estimates(Public Library of Science, 2021) Karunaweera, N.D.; Senanayake, S.; Ginige, S.; Silva, H.; Manamperi, N.; Samaranayake, N.; Dewasurendra, R.; Karunanayake, P.; Gamage, D.; de Silva, N.; Senarath, U.; Zhou, G.BACKGROUND: Leishmaniasis is a neglected tropical vector-borne disease, which is on the rise in Sri Lanka. Spatiotemporal and risk factor analyses are useful for understanding transmission dynamics, spatial clustering and predicting future disease distribution and trends to facilitate effective infection control. METHODS: The nationwide clinically confirmed cutaneous leishmaniasis and climatic data were collected from 2001 to 2019. Hierarchical clustering and spatiotemporal cross-correlation analysis were used to measure the region-wide and local (between neighboring districts) synchrony of transmission. A mixed spatiotemporal regression-autoregression model was built to study the effects of climatic, neighboring-district dispersal, and infection carryover variables on leishmaniasis dynamics and spatial distribution. Same model without climatic variables was used to predict the future distribution and trends of leishmaniasis cases in Sri Lanka. RESULTS: A total of 19,361 clinically confirmed leishmaniasis cases have been reported in Sri Lanka from 2001-2019. There were three phases identified: low-transmission phase (2001-2010), parasite population buildup phase (2011-2017), and outbreak phase (2018-2019). Spatially, the districts were divided into three groups based on similarity in temporal dynamics. The global mean correlation among district incidence dynamics was 0.30 (95% CI 0.25-0.35), and the localized mean correlation between neighboring districts was 0.58 (95% CI 0.42-0.73). Risk analysis for the seven districts with the highest incidence rates indicated that precipitation, neighboring-district effect, and infection carryover effect exhibited significant correlation with district-level incidence dynamics. Model-predicted incidence dynamics and case distribution matched well with observed results, except for the outbreak in 2018. The model-predicted 2020 case number is about 5,400 cases, with intensified transmission and expansion of high-transmission area. The predicted case number will be 9115 in 2022 and 19212 in 2025. CONCLUSIONS: The drastic upsurge in leishmaniasis cases in Sri Lanka in the last few year was unprecedented and it was strongly linked to precipitation, high burden of localized infections and inter-district dispersal. Targeted interventions are urgently needed to arrest an uncontrollable disease spread.Item Tissue impression smears as a supplementary diagnostic method for histopathology in cutaneous leishmaniasis in Sri Lanka(American Society of Tropical Medicine and Hygiene, 2018) Manamperi, N.H.; de Silva, M.V.C.; Pathirana, N.; Abeyewickreme, W.; Karunaweera, N.D.Cutaneous leishmaniasis (CL) is diagnosed mainly by light microscopy of smears made using lesion material. Histopathology is usually done in atypical presentations or when lesion smears are negative. Tissue impression smears (TIS) made from skin biopsy specimens were compared with histopathology for the diagnosis of CL. Out of the 111 patients included, 83 (74.8%) were positive by either methods. The TIS was positive in 70.3% whereas histopathology was positive in 56.8% of patients. Tissue impression smears can be used as a supplementary diagnostic test that gives sensitive and rapid results when tissue biopsies are used as the source of lesion material for diagnosis of CL.Item In situ immunopathological changes in cutaneous leishmaniasis due to Leishmania donovani(Oxford, Wiley, 2017) Manamperi, N.H.; Oghumu, S.; Pathirana, N.; de Silva, V.C.; Abeyewickreme, W.; Satoskar, A.R.; Karunaweera, N.D.INTRODUCTION: Cutaneous leishmaniasis in Sri Lanka is a newly established parasitic disease caused by the usually visceralizing Leishmania donovani. Skin lesions manifest as non-itchy, non-tender papules, nodules or ulcers. In situ cytokine expression provides clues for immunopathogenesis of this localized form of disease. METHODS: Skin biopsies from 58 patients were analyzed for histological appearance and in situ cytokine expression of T- helper 1 (Th1) and T- helper 2 (Th2) cytokines, namely interferon (IFN)-γ, interleukin (IL)-12A, tumor necrosis factor (TNF)-α, IL-4 and IL-10 by real-time RT- PCR. RESULTS: Significant up regulation of the Th1 cytokine IFN-γ and down regulation of the Th2 cytokine IL-4 was seen in patients compared to healthy controls. Significantly elevated tissue expression of IFN-γ and TNF-α was seen in lesions that presented later than 6 months from the time of onset, while IL-4 expression was more prominent in lesions that responded poorly to antimony therapy. CONCLUSION: A prominent Th1 response appears to support resolving of lesions, whereas a Th2 biased milieu tends to favor poor responsiveness to antimony and delayed lesion healing in L. donovani infections in Sri Lanka. This article is protected by copyright. All rights reserved.Item Larvivorous potential of the Guppy, Poecilia reticulata, in Anopheline mosquito control in river bed pools below the Kotmale dam, Sri Lanka(SAGE Publishing, 2008) Kusumawathie, P.H.D.; Wickremasinghe, A.R.; Karunaweera, N.D.; Wijeyaratne, M.J.S.The larvivorous potential of Poecilia reticulata was studied in the laboratory and in the field. In the laboratory, the number of anopheline larvae consumed per fish per day and the number of larvae in fecal matter per fish were determined. In the field study, 29 of 60 selected riverbed pools in Kotmale oya, below the Kotmale dam, were stocked with P reticulata, whereas the rest served as controls. Anopheline larval surveys were carried out starting from 1 day prior to stocking of fish and on selected days subsequently. P. reticulata consumed an average of 117 +/- 32.33 larvae per fish per day. Fecal matter of P. reticulata contained an average of 2.7 +/- 2.68 larvae per fish . There was a significant reduction in the number of pools positive for anopheline larvae (P < .001) after stocking fish and the number of larvae per pool (P < .001) and per 100 dips (P < .001) as compared with controlsItem Costs and effectiveness of application of Poecilia reticulata (guppy) and temephos in anopheline mosquito control in river basins below the major dams of Sri Lanka(Royal Society of Tropical Medicine and Hygiene, 2008) Kusumawathie, P.H.D.; Wickremasinghe, A.R.; Karunaweera, N.D.; Wijeyaratne, M.J.S.In this study we examined the costs and effectiveness of using larvivorous fish, Poecilia reticulata, and a chemical larvicide, temephos, in anopheline mosquito control in the riverbeds below the major dams in Sri Lanka. Five riverbeds below the dams, namely Laxapana, Kotmale 1, Kotmale 2, Nilambe, Rantembe and Victoria, were selected. Riverbed pools in Laxapana and Kotmale 1 were treated with P. reticulata; Rantembe and Victoria were treated with temephos; and Kotmale 2 and Nilambe were kept as controls. In each area, the anopheline larval density, before and after application of fish/temephos, was estimated. The cost of application of fish/temephos was estimated by activities involved for each treatment. After intervention, there was a significant reduction in anopheline larval density in the fish-treated areas compared with the temephos-treated and control areas. Application of P. reticulata was 2.67 times less costly than that of temephos. The cost of fish application can be further reduced if the community is involved in the applicationItem Impact of vitamin A supplementation on health status and absenteeism of school children in Sri Lanka(HEC Press, Australia, 2007) Mahawithanage, S.T.C.; Kannangara, K.K.; Wickremasinghe, R.; Chandrika, U.G.; Jansz, E.R.; Karunaweera, N.D.; Wickremasinghe, A.R.The objective of this study was to determine the impact of Vitamin A supplementation on health status and absenteeism of school children. A randomized double blind placebo controlled trial over a period of 13 months was conducted in a rural area of Sri Lanka involving 613 school children attending Grades 1-5 (aged 5 to 13 years). Children were assigned to either 200,000 IU of Vitamin A (n=297) or placebo (n=316) once every 4 months. Socio-demographic data were obtained at baseline, and anthropometry and haemoglobin concentrations were assessed at baseline and post intervention. Serum vitamin A concentrations were assayed by HPLC in a subgroup of children (n=193) before administration of each dose. School absenteeism was recorded. The two groups of children were similar at baseline in all variables. The subgroup of children was comparable to the main study population. The prevalence of vitamin A deficiency (< 20 microg/dL) in the subgroup of children was 8.2%. Changes in anthropometric indices and haemoglobin concentrations were similar in the two groups. The major causes for absenteeism were non-health causes and supplemented children lost a fewer number of school days due to illness than placebo children (p=0.053). Vitamin A concentrations improved with each dose and the improvement was greater with better compliance. Vitamin A supplementation with 200,000 IU every 4 months over 13 months improved vitamin A status and school attendance but not anthropometric status of these children.Item Larvivorous potential of fish species found in river bed pools below the major dams in Sri Lanka(Entomological Society of America, 2006) Kusumawathie, P.H.D.; Wickremasinghe, A.R.; Karunaweera, N.D.; Wijeyaratne, M.J.S.Malaria in Sri Lanka is closely associated with the river systems in the country. Construction of major dams across rivers has resulted in year-round pooling and anopheline mosquito breeding in river beds below the dams. This study was carried out to determine the larvivorous activity of fish found inriver bed pools below the dams to identify the potential fish species for anopheline larval control in these areas. Fish species in five river beds below the dams, namely, Laxapana, Kotmale, Nilambe, Victoria, and Rantembe, were identified in June 2000. The larvivorous potential of the 12 fish species collected was determined in the laboratory based on the number of larvae consumed per fish within 10 min and an hour. Danio malabaricus Jerdon, Oreochromis mossambicus Peters, Oreochromis niloticus L., and Poecilia reticulata Peters consumed nine or more larvae per fish within 10 min. Aplocheilus dayi Steindachner and Rasbora daniconius Hamilton consumed nine and eight larvae, respectively, within 1 h. O. mossambicus, O. niloticus, and P. reticulata consumed 10 larvae per fish within 10 min. Despite some species having a high larvivorous potential in the laboratory, field studies are required to determine the feasibility of using these fish for anopheline mosquito control in the river bed pools below the dams