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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Evidence of orthohantavirus and leptospira infections in small mammals in an endemic area of Gampaha district in Sri Lanka(BioMed Central Ltd, 2022) Sunil-Chandra, N.P.; Fahlman, A.; Waidyarathna, S.; Näslund, J.; Jayasundara, M.V.M.L.; Wesula, L.O.; Bucht, G.Background: Orthohantaviruses and leptospira are emerging zoonotic pathogens of high public health significance. The epidemiology of orthohantavirus infections and leptospirosis is similar and presents related clinical pictures in humans. However, a paucity of data on actual reservoir hosts for orthohantaviruses and leptospira exists. Therefore, this study aimed at determining the occurrence of orthohantaviruses and leptospira in small mammals captured in an endemic region of Sri Lanka. Methods: Rodents and shrews were morphologically and/or genetically identified using morphological keys and DNA barcoding techniques targeting the cytochrome oxidase b subunit gene (Cytb). Lung tissues and sera were subsequently analyzed for the presence of orthohantavirus RNA using qRT-PCR. Sera of rats were tested for IgG antibodies against orthohantaviruses and leptospira. Results: Forty-three (43) small mammals representing: Rattus (R.) rattus (black rat) or R. tanezumi (Asian rat), Suncus murinus (Asian house shrew), R. norvegicus (brown rat) and Mus musculus (house mouse) were investigated. No orthohantavirus RNA was detected from the lung tissue or serum samples of these animals. Elevated levels of IgG antibodies against Puumala orthohantavirus (PUUV) and/or Seoul orthohantavirus (SEOV) antigens were detected in sera of 28 (72%) out of the 39 rats analysed. Interestingly, 36 (92%) of the 39 rats also showed presence of anti leptospira-IgG antibodies in their serum, representing dual infection or dual exposure in 26/39 (66.7%) of examined rats. Conclusions: This project targets important public health questions concerning the occupational risk of orthohantavirus infections and/or leptospirosis in an endemic region of Sri Lanka. Most rats (72%) in our study displayed antibodies reacting to orthohantavirus NP antigens, related to PUUV and/or SEOV. No correlation between the orthohantavirus and leptospira IgG antibody levels were noticed. Finally, a combination of both morphological and DNA barcoding approaches revealed that several species of rats may play a role in the maintenance and transmission of orthohantavirus and leptospira in Sri Lanka.Item Corrigendum: Association of Hantavirus infections and Leptospirosis with the occurrence of Chronic Kidney Disease of Uncertain Etiology in the North Central Province of Sri Lanka: A Prospective study with patients and healthy persons(Frontiers Media SA, 2020) Sunil-Chandra, N.P.; Jayaweera, J.A.A.S.; Kumbukgolla, W.; Jayasundara, M.V.M.L.[This corrects the article doi: 10.3389/fcimb.2020.556737]. Erratum for : Association of Hantavirus infections and Leptospirosis with the occurrence of Chronic Kidney Disease of uncertain etiology in the North Central Province of Sri Lanka: A Prospective study with patients and healthy persons [Frontiers in Cellular and Infection Microbiology. 2020;10:556737].Item Association of Hantavirus infections and Leptospirosis with the occurrence of Chronic Kidney Disease of Uncertain Etiology in the North Central Province of Sri Lanka: A prospective study with patients and healthy persons(Frontiers Media SA, 2020) Sunil-Chandra, N.P.; Jayaweera, J.A.A.S.; Kumbukgolla, W.; Jayasundara, M.V.M.L.ABSTRACT: Chronic Kidney disease of uncertain etiology (CKDu) has become a significant disease burden, affecting farming community of Sri Lanka and the exact etiology, which could be multifactorial, is not hitherto established. This study is aimed to determine the association of past hantavirus infection and leptospirosis with the occurrence of CKDu. A cohort (n = 179) of known CKDu patients living in high-CKDu prevalent areas of Anuradhapura district of Sri Lanka was compared with a group of 49 healthy, sex-matched younger blood relatives of CKDu patients (control-1) and another 48 healthy, age, and sex-matched individuals living in low-CKDu prevalent area (control-2) of the same district where same life style and climate conditions prevail. Fifty out of 179 (27.9%) CKDu patients, 16/49 (32.7%) of control-1 and 7/48 (14.6%) of control-2 were found positive for IgG antibodies to Puumala, Hantaan or both strains of hantaviruses. Hantaan strain specificity was found to be predominant in all study groups. Hantavirus IgG sero-prevalence of healthy individuals living in low-CKDu prevalent area was significantly lower compared to CKDu patients and healthy younger blood relatives living in high-CKDu prevalent areas (p = 0.03). Past hantavirus infection possesses a significant risk for the occurrence of CKDu (OR = 4.5; 95% CI-3.1-5.4, p = 0.02). In contrast, IgG seroprevalence to hantaviruses was not significantly different in CKDu patients and healthy younger blood relatives living in high-CKDu prevalent areas indicating past hantavirus infection has no association with the occurrence of CKDu or possibly, younger relatives may develop CKDu in subsequent years. Seroprevalence to leptospirosis showed no significant difference between CKDu patients and healthy controls. KEYWORDS: CKDu; chronic kidney disease; hantaviruses; leptospira; sero-prevalence. Erratum in: Front Cell Infect Microbiol. 2020;10:631515Item Epidemiology of multidrug-resistant Enterobacteriaceae in Sri Lanka: First evidence of bla KPC harboring Klebsiella pneumoniae.(Elsevier., 2020) Kumudunie, W.G.M.; Wijesooriya, L.I.; Namalie, K.D.; Sunil-Chandra, N.P.; Wijayasinghe, Y.S.BACKGROUND: Extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-PE) and carbapenem-resistant Enterobacteriaceae (CRE) are disseminated worldwide posing a serious public health concern. Although, the presence of ESBL-PE and CRE in Sri Lanka has been reported, the prevalence is unknown. This study aimed to provide up-to-date epidemiological data on multidrug-resistant Enterobacteriaceae and to characterize the molecular determinants of carbapenemase-producing Enterobacteriaceae (CPE) in Sri Lanka.METHODS: A prospective cross-sectional study was conducted at a tertiary care hospital in Sri Lanka between December 2017 and February 2018. ESBL-PE and CRE were identified by disc diffusion method. Carbapenemase production was determined by carbapenem inactivation method and the presence of selected carbapenemase genes were detected by PCR. RESULTS: Five hundred and ninety-three Enterobacteriaceae were isolated from variety of clinical samples. Overall prevalence of ESBL-PE and CRE were 26.0% (n = 154) and 9.6% (n = 57), respectively. The highest rate of ESBL-PE (30.8%) was found in urine samples, while the highest occurrence of CRE (20.8%) was seen in respiratory specimens. The most common CRE species identified was K. pneumoniae (n = 46, 80.7%), followed by C. freundii (n = 4, 7.0%), E. coli (n = 3, 5.3%), P. rettgeri (n = 2, 3.5%), E. cloacae (n = 1, 1.7%), and K. aerogenes (n = 1, 1.7%). Carbapenemase production was observed in 54 (94.7%) of CRE isolates. Fifty eight carbapenemase encoding genes were identified in 54 CPE. The most prevalent carbapenemase gene was blaOXA-48-like (n = 48, 88.9%), followed by blaNDM (n = 8, 14.8%), and blaKPC (n = 2, 3.7%). CONCLUSIONS: This study reports an alarming rate of CRE and the emergence of blaKPC harboring K. pneumoniae in Sri Lanka. The need for preventive measures is highlighted to limit the spread of these difficult-to-treat bacteria in the country. KEYWORDS: Carbapenem resistance; Carbapenemase; ESBL; Enterobacteriaceae; KPC; Sri Lanka.Item Canine Rabies and its implications for human health in Sri Lanka(Veterinary Research Institute, 2018) Ubeyratne, J.K.H.; Srikitjakarn, L.; Pfeiffer, D.U.; Kohnle, L.; Sunil-Chandra, N.P.; Chaisowwong, W.; Hemwan, P.Rabies is an endemic viral zoonotic disease in Sri Lanka. Dogs are the main reservoir and transmitter, making surveillance of canine rabies crucial for disease elimination. Sri Lanka is one of the Asian countries where human deaths from rabies have been reduced markedly, but it still remains a significant public health problem. Ninety-five percent of human cases in the country are attributed to dog bites. Human settlement patterns allow the existence of dogs. The size of the dog populations is dependent on the habitat, especially the availability of resources such as food, water, and shelter. Although most dogs are owned, many ownerless dogs are allowed to roam freely resulting in vaccination coverage in dogs is heterogeneous. Other terms for ownerless dogs, i.e., dogs which do not have an acknowledged owner include community dogs and stray dogs. Such type of ownerless dogs are more common in rural as compared to urban areas. The frequency of vaccination in ownerless dogs is below the required level. Human attitudes towards dogs, especially ideas of responsible ownership, dog-keeping practices, and other aspects of human behavior influence rabies transmission risk. Research is required to reduce existing gaps in understanding of the knowledge, attitudes, and practices of the general population regarding the need for both dog population control and for rabies vaccination. Additionally, an improved understanding of dog demography and the ecological context of dog populations is essential for increasing dog vaccination coverage, achieving more effective vaccination campaign planning, and better determining the needs of dog population management programs. In order to achieve control of and finally eliminate rabies in Sri Lanka, the epidemiology of canine rabies in the country should be studied in relation to dog ecology and social aspects of pet ownership. A well-executed rabies control program needs to be based on integrated information regarding dog populations including an understanding of relevant differences in environmental habitats, in human cultures and social strata, and in different epidemiological situations. This article examines the rabies situation in Sri Lanka with respect to trends in human and canine rabies and identifies challenges ahead for rabies elimination.Item A Descriptive Study on Antibiotic Resistant, Clinically Significant Coliform Species Isolated from the Patients at Colombo North Teaching Hospital (CNTH), Ragama, Sri Lanka(19th Conference on Postgraduate Research, International Postgraduate Research Conference 2018, Faculty of Graduate Studies,University of Kelaniya, Sri Lanka, 2018) Wijesooriya, L.I.; Namalie, K.D.; Sunil-Chandra, N.P.Introduction: Antibiotic resistance (AR) is a great therapeutic challenge globally and locally today. The rate of development of AR is far ahead compared to the discovery of a new class of antibiotics, which has not been successful in last three decades. Of the antibiotic resistant coliforms, extended spectrum beta-lactamase producers (ESBLP) play a key role in life threatening infections. Moreover, emergence of carbapenem-resistant Enterobacteriaceae (CRE) has further limited the effective therapeutic options. Objective: To investigate the AR of clinically significant Enterobacteriaceae isolated from patients in a tertiary healthcare setting. Method: A descriptive, cross-sectional study was conducted involving patients with coliform infections at CNTH from 01/03/2018 to 31/08/2018. Demographic details, clinical data & antibiotic sensitivity test (ABST) patterns were analyzed. ABST was performed according to John-Stokes method & ESBLPwere identified by the keyhole method. Resistance to either meropenem or imipenem is used to identify CRE. Statistical analysis was done via R programming language (level of significance P<0.05). Results: Of the 200 coliforms, 85.5% (171/200) were from inpatients & the rest were from outpatients. Of the studied patients, 53.5% (107/200) were females & 46.5% (93/200) were males. Of the Enterobacteriaceae spp isolated, 48.5% (97/200) were from urine, 34.5% (69/200) from pus / wound swabs, 9.5% (19/200) respiratory samples, 3% (6/200) sterile fluids & stents, & 3% (6/200) from blood & CVP tips. As per ABST, about 90% were resistant to ampicillin. Resistance was 61-70% against cefuroxime (oral), ciprofloxacin & nalidixic acid, 60% for amoxiclav, 41-50% for cefotaxime, cefuroxime (intravenous), co-trimoxazole, levofloxacin, norfloxacin & ofloxacin, 31-40% for cefepime, ceftazidime, ceftriaxone & nitrofurantoin, 21-30% for gentamicin & piperacillin tazobactam & 0-10% for amikacin & meropenem. Of the coliforms, 29% (58/200) were ESBLP & 8% (16/200) were CRE. None of the ESBLP was CRE. Of CRE, 37% (10/16) were resistant to amikacin. However, 93.8% (15/16) of CRE were colistin sensitive. Conclusion: Majority of the isolates represented infections of the inward patients & there was no statistically significant difference between male & female proportions. Coliforms were detectedmostly from urine. Majority (>50%) of clinically significant Enterobacteriaceae were resistant to most of the oral antibiotics namely cefuroxime, ciprofloxacin, nalidixic acid & amoxiclav. Of the oral antibiotics, nitrofurantoin has the lowest resistance against Enterobacteriaceae. None of the antibiotics had 100% sensitivity against Enterobacteriaceae. Results indicate that ESBLP can be safely treated with carbapenems. Colistin will be an effective empiric antibiotic for CRE.Item Comparison of Three Carbapenemase Producing Enterobacteria (CPE) Detection Methods(19th Conference on Postgraduate Research, International Postgraduate Research Conference 2018, Faculty of Graduate Studies,University of Kelaniya, Sri Lanka, 2018) Kumudunie, W.G.M.; Wijayasinghe, Y.S.; Wijesooriya, W.R.P.L.I.; Sunil-Chandra, N.P.; Namalie, K.D.Introduction: The emergence of carbapenem resistant enterobacteria (CRE) is a critical and growing health threat, causing a failure of almost all the available antibiotics and limiting the effective therapeutic options. CRE has been reported all over the world including Sri Lanka. The carbapenem resistance in enterobacteria is mainly occurred due to the production of carbapenemases, the carbapenem inactivating enzymes. Therefore, accurate and timely detection of CPE is an important aspect to streamline the empiric antibiotic therapy. In this study, three CPE detection methods namely, Carba NP-rapid biochemical test, modified carbapenem inhibition method (MCIM) and modified Hodge test (MHT) were compared for the detection of CPE. Carba NP test is a rapid biochemical test that requires 2 hours or less. However, both MCIM and MHT require incubation of 18 – 24 hours. Objective: To compare theCarba NP-rapid biochemical test with the MCIM and MHT for the detection of CPE. Methodology: Fifty-eight clinically significant CRE isolates were recovered from clinical specimens from patients attended to North Colombo Teaching Hospital (NCTH)during December 2017 – February 2018. Antibiotic sensitivity testing for the screening of CRE was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Enterobacteria, resistant to at least one carbapenem antibiotic were considered as CRE. Carba NP test, MCIM and MHT were carried out for CRE isolates according to the CLSI guidelines. Statistical analysis was done using R programming language (level of significance P<0.05). Results: Of 58 CRE, 94.82% (55/58) were confirmed as CPE via both MCIM and MHT while 77.58% (45/58) were revealed as CPE by Carba NP test. There was a significant reduction of CPE detection by Carba NP method compared to MCIM and MHT(P=0.007). Conclusion: Of the three CPE detection methods, sensitivity was higher in MCIM and MHT compared to Carba NP – rapid biochemical test. Acknowledgement: Financial assistance by National Research Council, Sri Lanka (NRC 17-055) is acknowledged.Item The Effect of acyclovir on the acute and latent murine gammaherpesvirus-68 infection of mice(Sage Publishing, 1994) Sunil-Chandra, N.P.; Efstathiou, S.; Nash, A.A.Mice inoculated intranasally with murine gammaherpesvirus-68 were used to evaluate the efficacy of acyclovir (ACV) in the treatment of acute and latent infections. Effectiveness was measured by infectious virus assay of the lung (site of active replication) and infectious centre assay of spleen cells (site of latency). Intraperitoneal administration of ACV at 6-h intervals starting soon after inoculation was more effective in reducing infectious virus in the lung than was treatment with 12-hourly injections commencing 3 days post-infection.Item Pathogenesis of murine gammaherpesvirus infection in mice deficient in CD4 and CD8 T cells(American Society for Microbiology., 1993) Ehtisham, S.; Sunil-Chandra, N.P.; Nash, A.A.Murine gammaherpesvirus is a natural pathogen of wild mice. The virus infects alveolar cells and spleen cells during the primary infection and establishes a latent/persistent infection in B lymphocytes. Little is known about the immunological response to gammaherpesviruses during a primary infection. To address this issue, we investigated the pathogenesis of murine herpesvirus 68 (MHV-68) infection in mice deficient in CD4 or CD8 T-cell populations. Infection of the lung and spleen were greatly exacerbated in CD8-deficient mice, reflected by elevated virus titers in the lung and an increase in the number of infected splenocytes located around germinal centers. This finding contrasts with clearance of virus from the lung and spleen by day 12 postinfection in CD4-depleted animals. These data clearly indicate a major role for CD8 T cells in recovery from an acute MHV-68 infection. Whereas CD4 T cells fail to influence the course of infection in the lung, they do contribute to lymphoproliferation seen in the spleen (splenomegaly) during the primary infection. The significance of these results are discussed in relation to the immune response to other herpesviruses, in particular Epstein-Barr virus, with which MHV-68 shares similar molecular and biological properties.Item Leptospirosis versus hantavirus infections in the Netherlands and in Belgium, 2000 to 2014 [Letter to the editor](European Centre for Disease Prevention and Control (ECDC), 2014) Clement, J.; Van Esbroeck, M.; Lagrou, K.; Verschueren, J.; Sunil-Chandra, N.P.; Van Ranst, M.No Abstract Available. Comment on: The hanta hunting study: underdiagnosis of Puumala hantavirus infections in symptomatic non-travelling leptospirosis-suspected patients in the Netherlands, in 2010 and April to November 2011.Goeijenbierm M et al. Euro surveillance.2014;19(38):20878