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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Initial response to SARS-CoV-2 (COVID-19) outbreak in Sri Lanka; views of public health specialists through an International Health Regulations lens(Public Library of Science, 2023) Caldera, A.; Wickremasinghe, R.; Newby, G.; Perera, R.; Mendis, K.; Fernando, D.The COVID-19 pandemic affected Sri Lanka despite having developed an International Health Regulations (IHR) steering committee in 2016 and a national action plan for health security following the Joint External Evaluation in 2018. Many steps were taken to improve the disaster management skills of healthcare workers even before the COVID-19 outbreak. We interviewed seven public health specialists to obtain their views on the country's response to the pandemic. A thematic analysis was conducted, leading to the emergence of three major themes and seven subthemes. The major themes included health security preparedness; COVID-19 management; and effects of COVID-19. The subthemes were; preparedness prior to pandemic and gaps in the preparedness (under health security preparedness); dual burden for the curative sector, strategies to reduce transmission and barriers to managing COVID-19 (under COVID-19 management) and negative and positive effects of COVID-19 (under effects of COVID-19). When COVID-19 reached Sri Lanka, healthcare workers, border control authorities and those involved with infectious disease control were overwhelmed by the magnitude of the pandemic. Healthcare workers' hesitation to work amidst the pandemic due to fear of infection and possible transmission of infection to their families was a major issue; the demand for personal protective equipment by health workers when stocks were low was also a contributory factor. Lockdowns with curfew and quarantine at government regulated centers were implemented as necessary. Perceptions of the public including permitting healthcare workers to perform field public health services, logistical barriers and lack of human resources were a few of the barriers that were expressed. Some persons did not declare their symptoms, fearing that they would have to be quarantined. The pandemic severely affected the economy and Sri Lanka relied on donations and loans to overcome the situation. Pandemic also brought about innovative methods to maintain and upgrade health service provision. Individuals with non-communicable diseases received their regular medications through the post which reduced their risk of being infected by visiting hospitals. Improvement of laboratory services and quarantine services, a reduction of acute respiratory infections and diarrhoeal diseases, improved intersectoral coordination and public philanthropic response were other positive effects.Item Reactive Case Detection (RACD) and foci investigation strategies in malaria control and elimination: a review(BioMed Central, 2020) Perera, R.; Caldera, A.; Wickremasinghe, A.R.BACKGROUND: Reactive case detection (RACD) and foci investigation are key strategies in malaria elimination and prevention of its re-establishment. They are a key part of surveillance that has been recommended by the World Health Organization (WHO) to be considered as a core intervention and as one of the three pillars of the Global Technical Strategy for Malaria 2016-2030. METHODS: A search using the key words "Reactive Case Detection", "RACD", "RCD" and "Malaria" was carried out in PubMed, Scopus, Taylor and Francis online databases for studies published until 31st July 2019. The inclusion criteria for selection of articles for review included (1) how RACD is implemented in each country; (2) challenges faced in RACD implementation; (3) suggestions on how the effectiveness of RACD process can be improved. RESULTS: 411 titles were identified, 41 full text articles were screened and 29 were found eligible for inclusion in the review. Published literature on RACD, and case and foci investigations has mostly assessed the process of the activity. Most studies have documented that the yield of positives in RACD has been highest in the index case's household and the immediate neighbourhood of the index case. Microscopy and RDTs are the common tests used in RACD. The guidelines for case and foci investigation, and RACD and PACD, are not universally adopted and are country-specific. Some of the limitations and challenges identified include lack of proper guidelines, logistic issues and problems with public compliance. CONCLUSIONS: Although there is no documented evidence that RACD is useful in malaria elimination settings, most authors have opined that RACD is necessary for malaria elimination. Lack of knowledge in the target populations, a target radius and how to carry out the RACD process is a major challenge in the decision-making process. KEYWORDS: 1-3-7 strategy; Foci investigation; Malaria control; Malaria elimination; Reactive case detection.Item Mitochondrial metabolic genes provide phylogeographic relationships of global collections of Aedes aegypti (Diptera: Culicidae)(Public Library of Science, 2020) Fernando, H.S.D.; Hapugoda, M.; Perera, R.; Black Iv, W.C.; de Silva, B.G.D.N.K.ABSTRACT: Phylogeographic relationships among global collections of the mosquito Aedes aegypti were evaluated using the mitochondrial Cytochrome C Oxidase 1 (CO1) and NADH dehydrogenase subunit 4 (ND4) genes including new sequences from Sri Lanka. Phylogeographic analysis estimated that Ae. aegypti arose as a species ~614 thousand years ago (kya) in the late Pleistocene. At 545 kya an "early" East African clade arose that continued to differentiate in East Africa, and eventually gave rise to three lineages one of which is distributed throughout all tropical and subtropical regions, a second that contains Southeast Asian/Sri Lankan mosquitoes and a third that contains mostly New World mosquitoes. West African collections were not represented in this early clade. The late clade continued to differentiate throughout Africa and gave rise to a lineage that spread globally. The most recent branches of the late clade are represented by South-East Asia and India/Pakistan collections. Analysis of migration rates suggests abundant gene flow between India/Pakistan and the rest of the world with the exception of Africa.Item Gene flow patterns among Aedes aegypti (Diptera: Culicidae) populations in Sri Lanka(MDPI AG, 2020) Fernando, H.S.D.; Hapugoda, M.; Perera, R.; Black Iv, W.C.; de Silva, B.G.D.N.K.ABSTRACT:In Sri Lanka, dengue is the most serious arboviral disease. Recent increases in dengue cases suggest a higher infection rate and spread of the disease to new areas. The present study explores gene flow patterns of Ae. aegypti, the main vector of dengue disease, among 10 collection sites including major ports and inland cities using variations at 11 microsatellite loci. Discriminant analysis of principal components (DAPC) and k-means clustering estimated eight genetic clusters. Analysis of Molecular Variance (AMOVA) estimated equal variances among cities and among collections in Colombo, Sri Lanka. Significant evidence, although weak, was detected for isolation by distance. Analysis of gene flow rates and directions using MIGRATE-n indicated that populations throughout the island served as a source of immigrants for Colombo with abundant gene flow among major commercial cities in Sri Lanka, which appear to receive migrant mosquitoes from throughout Sri Lanka. The observed patterns probably arise through human movement of Ae. aegypti during commerce from throughout Sri Lanka into Colombo increasing the risk of spread. The patterns uncovered in this study are significant for global health as Sri Lanka is situated along a key international shipping route. KEYWORDS: Aedes aegypti; Sri Lanka; gene flow patterns; population structure.Item First report of V1016G and S989P knockdown resistant (kdr) mutations in pyrethroid-resistant Sri Lankan Aedes aegypti mosquitoes(BioMed Central, 2018) Fernando, S.D.; Hapugoda, M.; Perera, R.; Saavedra-Rodriguez, K.; Black WC 4th; de Silva, N.K.; ; ;BACKGROUND: Dengue is a serious arboviral disease in Sri Lanka with a large number of dengue fever (DF) cases every year. Control of the primary vector Aedes aegypti depends upon larval habitat source reduction and insecticide application. However, increases in the number of reported cases suggest the inefficiency of current control strategies and the possibility of resistance to currently used insecticides. Early detection of mutations in the voltage-gated sodium channel (vgsc) gene that confer knockdown resistance (kdr) to pyrethroid insecticides is important in resistance management in vector populations. RESULTS: Resistance to pyrethroid insecticides was detected in the three populations studied. Polymerase chain reaction was used to detect the presence of two kdr mutations F1534C and V1016G. During this process a S989P mutation was also detected in pyrethroid-resistant Ae. aegypti populations. These mutations were found to be widespread and frequent in the collections studied. CONCLUSIONS: To our knowledge, this study reveals for the first time the presence of V1016G and S989P mutant alleles in the vgsc of Sri Lankan Ae. aegypti populations. The spread of the mutant alleles throughout the country poses a threat of increased resistance to pyrethroids. Long-term insecticide applications and indiscriminate use of pyrethroids has led to the evolution of resistance. More strategic and diverse strategies, including novel insecticides with new modes of action and community participation, should be engaged for Ae. aegypti control.Item Incidence and risk factors for non-alcoholic fatty liver disease: A 7-year follow-up study among urban, adult Sri Lankans(Blackwell Munksgaard, 2017) Niriella, M.A.; Pathmeswaran, A.; de Silva, S.T.; Kasturiratne, A.; Perera, R.; Subasinghe, C.E.; Kodisinghe, K.; Piyaratna, C.; Rishikesawan, V.; Dassanayake, A.S.; de Silva, A.P.; Wickremasinghe, R.; Takeuchi, F.; Kato, N.; de Silva, H.J.BACKGROUND: This study investigated incidence and risk factors for NAFLD among an adult cohort with 7-year follow-up. METHODS: The study population (age-stratified random sampling, Ragama MOH area) was screened initially in 2007 (aged 35-64 years) and re-evaluated in 2014 (aged 42-71 years). On both occasions assessed by structured interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. NAFLD was diagnosed on ultrasound criteria, safe alcohol consumption and absence of hepatitis B/C markers. Non-NAFLD controls did not have any ultrasound criteria for NAFLD. An updated case-control genetic association study for 10 selected genetic variants and NAFLD was also performed. RESULTS: Out of 2985 of the original cohort, 2148 (72.0%) attended follow-up (1238 [57.6%] women; mean-age 59.2 [SD-7.6] years) in 2014, when 1320 (61.5%) were deemed NAFLD subjects. Out of 778 who initially did not have NAFLD and were not heavy drinkers throughout follow-up, 338 (43.4%) (221 [65.4%] women, mean-age 57.8 [SD-8.0] years) had developed NAFLD after 7-years (annual incidence-6.2%). Central obesity (OR=3.82 [95%-CI 2.09-6.99]), waist increase >5% (OR=2.46 [95%-CI 1.20-5.05]) overweight (OR=3.26 [95%-CI 1.90-5.60]), weight gain 5%-10% (OR=5.70 [95%-CI 2.61-12.47]), weight gain >10% (OR=16.94 [95%-CI 6.88-41.73]), raised plasma triglycerides (OR=1.96 [95%-CI 1.16-3.29]) and diabetes (OR=2.14 [95%-CI 1.13-4.06]), independently predicted the development of incident NAFLD in multivariate analysis. The updated genetic association study (1362-cases, 392-controls) showed replicated association (P=.045, 1-tailed) with NAFLD at a candidate locus: PNPLA3 (rs738409). CONCLUSIONS: In this community cohort study, the annual incidence of NAFLD was 6.2%. Incident NAFLD was associated with general and central obesity, raised triglycerides and diabetes, and showed a tendency of association with PNPLA3 gene polymorphisms.Item A journey through history, religion, mythology and evolution(Sri Lanka College of Microbiologists, 2015) Perera, R.Abstract availableItem Classic polyarteritis nodosa associated with hepatitis C virus infection: a case report(BioMed Central, 2012) Rodrigo, D.; Perera, R.; de Silva, J.INTRODUCTION: Hepatitis C virus has been under-recognized as an etiologic factor for polyarteritis nodosa and the presence of hepatitis C antigenemia in patients with polyarteritis nodosa has been reported as insignificant. In the literature hepatitis C virus-associated polyarteritis nodosa is a rare and controversial entity. CASE PRESENTATION: A 34-year-old Sri Lankan Tamil man presented to our facility with a two-week history of slow-resolving pneumonia of the right mid and lower zones. On physical examination he had panniculitic type tender skin nodules with background livedo reticularis. A skin biopsy was suggestive of a small and medium vessel vasculitis compatible with polyarteritis nodosa. He was tested positive for hepatitis C antibodies. A serum cryoglobulin test was negative but perinuclear antineutrophilic cytoplasmic antibody test was positive. Serum complement levels were reduced. He was diagnosed as having classic polyarteritis nodosa associated with hepatitis C infection. He later developed left-sided radiculopathy involving both upper and lower limbs and an ischemic cardiac event. His hepatitis C infection was managed with polyethylene glycol-interferon 2α combined with oral ribavirin. Simultaneously, his classic polyarteritis nodosa was treated with prednisolone and cyclophosphamide. He made a good recovery. CONCLUSIONS: Hepatitis C virus infection is capable of inducing a fulminant form of vasculitis in the form of polyarteritis nodosa. It may be easily confused early in its course with mixed cryoglobulinemia, which is commonly known to be associated with hepatitis C virus. Awareness of hepatitis C virus-related polyarteritis nodosa helps in diagnosing the condition early so combined immunosuppressive and antiviral treatment can be started as soon as possible