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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty

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    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.
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    Histopathology of cutaneous leishmaniasis caused by Leishmania donovani in Sri Lanka.
    (Hindawi Pub. Co., 2020) Wijesinghe, H.; Gunathilaka, N.; Semege, S.; Pathirana, N.; Manamperi, N.; de Silva, C.; Fernando, D.
    ABSTRACT: Cutaneous leishmaniasis (CL) is a neglected tropical disease that is gaining importance in Sri Lanka and internationally. The clinical presentation, pathology, and method of parasite elimination in CL vary according to the species. Leishmania donovani is the causative organism for leishmaniasis in Sri Lanka. This collaborative cross-sectional study describes the clinicopathological features of cutaneous leishmaniasis among personnel of the tri-forces serving in the North and East of the country. The histology of fifty cases of CL confirmed by at least two methods (slit skin smear, lesion aspirate, tissue impression, and histology) was reviewed. The parasitic load was assessed semiquantitatively. The histological features were correlated with the clinical presentation and organism load. The majority (89.8%; n = 44) presented with a single lesion mostly located in the upper limb (69.4%). The lesion types included papule (34.7%), nodule (32.7%), and an ulcer (30.6%). The evolution time of lesions averaged 31.55 weeks. Epidermal changes were observed in 49 of the biopsies and included hyperkeratosis (90.0%; n = 45), acanthosis (44.0%; n = 22), atrophy (34.0%; n = 17), and interface change (66%; n = 33). Dermal changes were seen in all cases and were characterized by a lymphohistioplasmacytic inflammatory infiltrate of variable intensity with ill-formed granuloma in 19 cases (38%) and well-formed epithelioid granulomas in 22 cases (44%). Focal necrosis was present in 20% (n = 10). Leishmania amastigote forms were observed in 88% (n = 44). Transepidermal elimination (P = 0.025), granuloma (P = 0.027) formation, and type of lesion (P = 0.034) were significantly associated with the organism load. Granuloma formation was associated with a reduction in organism load, indicating that the macrophage activation played an important role in the control of the organism.
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    Prevalence of cutaneous leishmaniasis infection and clinico-epidemiological patterns among military personnel in Mullaitivu and Kilinochchi districts of the Northern Province, early war-torn areas in Sri Lanka.
    (BioMed Central, 2020) Gunathilaka, N.; Semege, S.; Pathirana, N.; Manamperi, N.; Udayanga, L.; Wijesinghe, H.; Premaratne, P.; Fernando, D.
    BACKGROUND: The 30-year-old armed conflict in Sri Lanka resulted in a general breakdown of civil administration in the Northern and Eastern provinces, leading to mobilisation of many armed forces personnel to assist with reconstruction and resettlement. This occupational group has been identified as a priority risk group for leishmaniasis. METHODS: Individuals enlisted at all military establishments in Mullaitivu and Kilinochchi districts, Northern Province of Sri Lanka were included. Five thousand individuals were screened for skin lesions between September 2018 and August 2019. Persons with lesions suspected as cutaneous leishmaniasis (CL) were further investigated. Information on sociodemographic/other potential risk factors was obtained through an interviewer-administered structured questionnaire. The diagnosis was confirmed by microscopic visualization of parasitic stages from different samples obtained (skin scraping, lesion aspirate and tissue impression smears), histopathology and polymerase chain reaction DNA amplification. RESULTS: Among 5000 individuals screened, 74 individuals were suspected of having CL. Of these, 67.6% (n = 50) patients were confirmed for CL by microscopy. Around two third of both males (67.6%; n = 48) and females (66.6%; n = 2) were positive for Leishmania. The soldiers belonging to 26-35-year age group reported the highest susceptibility (83.3%; OR: 4.83, 95% CI: 3.49-6.20%). Of the sociodemographic factors, age, wearing short-sleeved upper body clothing as the uniform and non-use of insect repellents were identified as significant risk factors. Most of the CL patients had a single lesion (86.0%; n = 43) of an ulcerative type (34.0%; n = 17), mostly on their upper limb (67.9%; n = 34). Lesions were mostly 5-10 mm diameter (59.9%; n = 30) in size with poorly defined margins (72.0%; n = 36). Amongst the diagnostic techniques, microscopic examination of slit skin smear and tissue impression smear were able to discriminate the majority of patients (92.1%; n = 46) for CL. CONCLUSIONS: In order to highlight the true burden of leishmaniasis in the military personnel, cases of leishmaniasis from military institutes should be recognized as a different entity per say and be included in the national figures so as to depict the real magnitude of the disease burden amongst this high-risk group. KEYWORDS: Clinical; Cutaneous leishmaniasis; Epidemiological; War-torn areas.
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    Diurnal adult resting sites and breeding habitats of Phlebotomine sand flies in Cutaneous Leishmaniasis endemic areas of Kurunegala District, Sri Lanka
    (BioMed Central, 2020) Wijerathna, T.; Gunathilaka, N.
    BACKGROUND: Sand flies are responsible for the transmission of several disease pathogens including Leishmania. Sand flies breed in habitats with high levels of humidity and organic matter. They are nocturnal in nature and peak activity ranges from dusk to dawn. The scientific evidence on breeding ecology and diurnal resting sites of sand fly fauna are important aspects of planning and implementing vector control activities. However, such fundamental information is grossly inadequate in Sri Lanka to support the control efforts in the country. Therefore, the present study addresses some of the important aspects of sand fly breeding ecology and diurnal resting sites. METHODS: Potential resting sites were thoroughly observed, and sand flies were collected using a battery-operated aspirator and sticky papers when appropriate from three selected Medical Officer of Health (MOH) areas (Polpithigama, Maho and Galgamuwa) in Kurunegala district, Sri Lanka. Soil samples were collected from each potential breeding site. Half of each soil sample was incubated for 45 days. The other half was screened for immature stages. Adult sand flies collected from field and emerged adults at the insectary under confined incubation were identified using morphological characteristics. RESULTS: Pepper bushes and termite mounds were the most notable resting sites while, betel bushes, cattle huts, piles of coconut shells, latrines, manna bushes and tree holes were also positive for sand fly adults. Only two species, Phlebotomus argentipes and Sergentomyia punjabensis, were reported. Soil samples were collected from a total of 432 sites and 7 of them were positive for immature stages. Predominant breeding habitats identified during the present study were mud flats and moist soils of rice paddies, the soil below decaying hay, drying irrigational tank bottom moist soil, and the floors of cattle huts. CONCLUSIONS: This study demonstrates that the potential adult resting sites and breeding habitats are abundant in the Polpithigama, Maho and Galgamuwa MOH areas. Therefore, vector control activities targeting both adult and immature stages of sand flies are recommended. KEYWORDS: Breeding sites; Leishmaniasis; Resting sites; Sand fly; Sri Lanka.
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    The Economic Impact of Cutaneous Leishmaniasis in Sri Lanka.
    (Hindawi Publishers, 2018) Wijerathna, T.; Gunathilaka, N.; Gunawardena, K.
    Cutaneous leishmaniasis (CL) is a neglected tropical disease which affects mainly the poorest communities in developing countries. Considering the limited published information on economic impact of CL in Sri Lanka, the current study was conducted with the objective of revealing the nature and magnitude of the economic impact of CL in three selected disease endemic regions in Kurunegala District, Sri Lanka. The patient records of CL notified of relevant Medical Officer of Health (MOH) office during 2013- 2016 were obtained. Patient households were visited and data collection was done using an interviewed administered questionnaire. The majority of patients (57%) were economically active at the time of infection. Of them, 65% were the only contributors to household economy. Total median costs including both direct and indirect costs were 66.85 USD (Rs. 10,831) (IQR = 57.26 - 86.78 USD), while total median economic loss to households was 61.27 USD (Rs. 9,927) (IQR= 49.61- 75.04 USD). From provider perspective, total median cost per patient was 22.83 USD (Rs. 3,696). The mean total economic loss was denoted as 65.26 USD (Rs. 10,572) which is about 5.4% of the annual household income and 20.9% of the mean annual per capita income of the study population. Although economic impact of CL infection is not catastrophic according to current interpretation, the infection may have significant economic impacts on households when considering the mean economic loss to household as a percentage of the mean annual per capita income of the population.
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    Evaluation of rapid extraction and isothermal amplification techniques for the detection of Leishmania donovani DNA from skin lesions of suspected cases at the point of need in Sri Lanka
    (BioMed Central, 2018) Gunaratna, G.; Manamperi, A.; Bohiken-Fascher, S.; Wickremasinghe, R.; Gunawardena, K.; Yapa, B.; Pathiana, N.; Pathirana, H.; de Silva, N.; Sooriyaarachchi, M.; Deerasinghe, T.; Mondal, D.; Ranasinghe, S.; Abd EI Wahed, A.
    BACKGROUND: Leishmaniasis is a disease caused by vector-borne protozoans. In Sri Lanka, the cutaneous form of the disease is predominant, which is usually diagnosed using Giemsa-stained slit skin smear examination and by histology. However, the sensitivity of slit skin smears and histology are reportedly low. Moreover, facilities for the highly sensitive polymerase chain reaction (PCR) are available only in a few highly-equipped parasitology laboratories. Therefore, there is a need for low cost, sensitive and specific screening tests for diagnosis of leishmaniasis at the point of need. RESULTS: In this study, a mobile suitcase laboratory applying novel extraction (SpeedXtract) and isothermal amplification and detection (recombinase polymerase amplification assay, RPA) methods were evaluated for the diagnosis of cutaneous leishmaniasis in Sri Lanka. First, the developed assay was applied to three different sample types (punch biopsy, slit skin smears and fine needle aspirates) at a local hospital. The results showed that the 2 mm punch biopsy sample produced the best exponential amplification curve and early fluorescence signal in the RPA assay. Secondly, punch biopsies were collected from 150 suspected cutaneous leishmaniasis cases and screened with SpeedXtract/RPA, RNAlater/PCR and ATL buffer/PCR, in addition to Giemsa-stained slit skin smears. Fifty-seven samples were negative in all detection methods. In total 93 samples were positive with assay sensitivities of 65.5% (SpeedXtract/RPA), 63.4% (RNAlater/PCR) and 92.4% (ATL buffer/PCR). The Giemsa-stained slit skin smear delivered the worst clinical sensitivity (32.2%). CONCLUSIONS: The SpeedXtract/RPA method under field conditions took 35 min, while almost 8 h were needed to finalize the extraction and detection by PCR in the laboratory. The SpeedXtract/RPA method produced similar sensitivity to samples preserved in RNAlater and subjected to PCR amplification, but both were less sensitive than ATL-preserved samples subjected to PCR amplification. There is a need for a standardization of sample collection and nucleic acid extraction methods.
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    Clinical and histopathological characteristics of cutaneous leishmaniasis in a group of military personnel in Sri Lanka
    (American Society of Tropical Medicine and Hygiene, 2015) Manamperi, N.H.; Fernando, C.S.; Pathirana, A.; Abeyewickreme, W.; de Silva, V.C.; Karunaweera, N.D.
    Cutaneous leishmaniasis (CL) is a newly established vector-borne parasitic disease in Sri Lanka. Military personnel have an occupational risk for CL due to being stationed in endemic areas and exposure to vectors outdoors. This study describes the clinical and histopathological features of CL in a group of military personnel. Thirty five patients with smear positive for Leishmania amastigotes were included, their data analyzed for clinical features and skin biopsies processed routinely for histology, examined at a conference microscope and classified into 4 groups using modified Ridley criteria for Leishmaniasis as: I-parasitized macrophages with variable lymphocytes and plasma cells; II-parasitized macrophages with lymphocytes, plasma cells and ill formed histiocytic granulomata; III-a mixture of macrophages (with or without parasites), lymphocytes, plasma cells and epithelioid granulomata; IV-epithelioid granulomatous response with a few lymphocytes and plasma cells but no amastigotes. Lesions were categorized by duration, as acute (< 6 months) or chronic (> 6 months). Study group composed of all males with a mean age of 32.6 years (range 22-47) and lesion duration of 5.6 months (range 1-24). Number of lesions varied from 1 to 6 with majority (71.4%, n= 25) having a single lesion. Nodular (37.1%, n=13) and nodulo-ulcerative (25.7%, n=9) lesions in upper limbs (68.6%, n=24) was the commonest presentation. Twenty nine (82.9%) of the biopsies were positive also by histology. Twenty two (62.9%) were acute and 13 (37.1%) chronic. Group I, II, III and IV patterns were seen in 14 (40%), 12 (34.3%), 5 (14.3%) and 4 (11.4%) respectively and 9 (40.9%), 9 (40.9%), 2 (9.1%) and 2 (9.1%) of acute lesions and 5 (38.5%), 3 (23.1%), 3 (23.1%) and 2 (15.4%) of chronic lesions respectively. Necrosis was not seen in any of the lesions. Majority in this group of military personnel with CL had single lesions affecting the upper limbs and sought treatment within 2 years of appearance of lesions. The histological picture varied from diffuse infiltration of parasitized macrophages admixed with chronic inflammatory cells to ill-formed histiocytic granulomata.
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    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.
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