Theses - Faculty of Medicine
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Item Molecular characterization of carbapenemase producing enterobacteria (CPE) isolated from a tertiary care teaching hospital in Sri Lanka and validation of a rapid CPE detection protocol(University of Kelaniya, Sri Lanka, 2021) Kumudunie, W.G.M.INTRODUCTION: The emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) is in dramatic increase, resulting in failure of almost all the available antibiotics and hence limit the effective therapeutic options. Therefore, accurate and timely detection of carbapenemase-producing enterobacteria (CPE) is essential to streamline the optimum antibiotic therapy. This study was carried out to determine the current status of CRE in Sri Lanka and to evaluate the performances of CPE detection methods. METHODOLOGY: A cross-sectional study was conducted at Colombo North Teaching Hospital during 2017-2018. Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) and CRE were identified by the disc diffusion method. CRE isolates were identified up to species level using a rapid identification kit. Four CPE detection methods, namely Carba NP test (CNPt), CNPt-direct, modified carbapenem inhibition method (mCIM), and modified hodge test (MHT) were evaluated. The genetic background of CPE was determined by PCR. RESULTS: The estimated overall prevalence of ESBL-PE and CRE were found to be 26.0% and 9.6%, respectively. The highest prevalence of ESBL-PE and CRE were found amongst uropathogenic (30.8%) and respiratory infections producing (20.8%) Enterobacteriaceae, respectively. K. pneumoniae (80.7%), E.coli (5.3%), C.freundii (7.0%), P. rettgeri (3.5%), E. cloacae (1.7%), and E. aerogenes (1.7%) were identified in CRE cohort. OfCRE, 94.7% were found to be CPE. The carbapenemase encoding genes detected were of blaKPc, blCINDM. and blaoXA-48-Iike and, blaoXA-48-Iike (88.9%) was the most prevalent. The overall sensitivity and specificity of CPE detection tests were as; MHT-90.7%, 92.1%, mCIM- 100%, 100%, CNPt-75.9%, I 00%, and CNPt-direct-83.3%, 100%, respectively. Only amikacin showed reasonable sensitivity (>50%) for CRE among the routine antibiotic panel whereas a higher level of susceptibility was noted for fosfomycin (92.9%), ceftazidime-avibactam (85.9%), and colistin (92.9%). CONCLUSION: K pneumoniae was the most prevalent CRE species. Carbapenemases production was the major resistance mechanism in CRE and b/aoXA-48-like was the most prevalent gene type. The first occurrence of blaKPc was recognized in Sri Lanka. MCIM and MHT had higher sensitivity compared to both CNP tests for the detection of CPE. However, when a prompt decision is needed, CNP tests can be a viable option since their results can be obtained within two hours.Item Social anxiety disorder among university students in Sri Lanka : prevalence, associated risk factors, and culturally adapted cognitive behavioural group therapy(University of Kelaniya, Sri Lanka, 2022) de Silva, B.G.R.Social Anxiety Disorder (SAD), one of the most common mental health disorders globally, demonstrate early-onset, chronic course, and debilitating dysfunction in all social spheres, especially in education. There is a scarcity of information on SAD in Sri Lanka, and none among university students. Therefore, the study objectives were to determine prevalence and associated risk factors among university students in Sri Lanka. A cross-sectional study was conducted among 1137 students from five state universities. The Liebowitz Social Anxiety Scale — Sinhala version and a Psychosocial Correlates Questionnaire for SAD developed for this study, were used as instruments. The analysis included bivariate analysis such as chi-square tests for independence, and Spearman’s r correlations to identify significant associations. Identified variables at p<0.05 were entered in to binary logistic regression models to determine factors associated with social anxiety disorder. Of the 985 who completed the questionnaires, 57.1% screened positive for SAD. In terms of demographic factors and _ clinical characteristics, female gender(AOR=1.41,95%CI 1.10-1.84, p= 0.01) and a history of mental health issues(AOR=2.79, 95%CI 1.90-4.10, p<0.001), and in terms of negative family and adverse childhood experiences, experiences of emotional abuse(AOR=1.31, 95% CI 1.11- 1.54, p=0.001), parent dissatisfaction (AOR=1.07, 95% CI 1.01- 1.13, p<0.05) and overcontrol by parents(AOR=1.08,95%CI1.02-1 .15,p<0.05) remained significantly associated risk factors for SAD. Further, | body dissatisfaction (AOR=1 .05, 95% CI 1.05 — 1.10, p<0.05) , and dissatisfaction with breasts (AOR=.60, 95% CI .46 — .77, p<0.001) were identified as associated significant factors of SAD. Additionally, in terms of school experiences, experiences of humiliation, not being accepted or rejection by school friends (AOR=1.63,95% Cr 1.29-2.05, p<0.001) and rejection, invalidation or isolation due to social connections(AOR=1.3, 95% Cl 1.08- 1.58, p<0.001) , while in university experiences, experiences of humiliation, not being - accepted or rejection by friends(AOR=1.31,95%CI1.09-1.60,p<0.05), experiences of mental harassment(AOR=1.47,95%CI 1.12-1.92,p<0.05), and viewing the medium of study as a challenge,(AOR=1.55,95%CI1.16-2.10,p<0.05) remained independently and significantly associated with SAD. The study recognizes a high prevalence rate of SAD and associated risk factors among university students in Sri Lanka. Although, diagnostic interviews were not conducted — and the actual prevalence rates may be lower, this is an under-recognized issue which needs further exploration as students with SAD will be challenged in their academic and occupational pursuits.Item Biochemical,inflammatory, and histopathological changes in wistar rats given dug well water from high and low disease prevalent villages for chronic kidney disease of unknown etiology (CKDu) in north central province of Sri Lanka(University of Kelaniya, Sri Lanka, 2021) Thammitiyagodage, M.G.Chronic Kidney Disease of unknown etiology (CKDu) is prevalent in the North Central Province (NCP) of Sri Lanka. Ingestion of groundwater is identified as one of the causative factors. The einfonley of the population consumes un-boiled dug well water. The objectives of the study were to find out the biochemical, haematological, and immunological changes in Wistar rats that ingested dug well water from high and low disease prevalent areas from the NCP and low disease prevalent Colombo and correlate the findings with their histopathological changes. Sex balance 3 months old Wistar rats (n=60) were used for the study. Their WBC/ DC, cpt CD** gerum cytokines, creatinine, ALT, AST, BUN levels and Microalbumin: creatinine ratios were measured. Rats were randomly divided into 6 groups by assigning 10 rats per group. Groups 1, 2, and 3 were given water from high disease prevalent New Town Medirigiriya (NTM), Bisobandaragama (BB), and Divuldamana (DD) respectively. Group 4 was given boiled water from NTM (NTMB). Groups 5 and 6 were given water from low disease prevalent Huruluwewa (HW) from NCP and tap water from low disease prevalent Colombo (CO) adlibitum quantity. Serum cytokines (IL1β; IL6, TNFα) were measured after 8 months and CD 4+ and CD 8+ counts were measured after 14 months. Histopathology was performed in kidney and liver tissues. Serum TNFα levels were significantly elevated in rats from DD and BB (p<0.05) but hepatic TNFα levels were significantly elevated only in rats from DD (p<0.05)). Rats from high disease prevalent NTM had significantly high CD4+ and CD8+ cells than those from low disease prevalent HW and CO. Immunological findings. were correlated with the histopathological changes. There was a correlation between the kidney Tubular Interstitial (TI) Lesion index and liver lesions. Serum TNFα and CD4+ and CD8+ lymphocytes were closely correlated with renal damage. Rats with severe TI lesions reported a high percentage of portal tracts and parenchymal lesions in the liver and this expression was minimum in CO. It was evident that boiling water was effective against liver damage but not renal damage. The present study is supportive of an immune therapy targeting the CD4+ and CD8+, and TNFα in reducing renal damage in the early stages of the disease. In conclusion, peritubular nonsuppurative interstitial cell infiltrations in kidney tissues were common in all the experimental groups irrespective of the toxicant sicient in water bodies. Observed kidney damage may mediate via cytokine triggered immune response by high sodium, fluoride, calcium and some other unmeasured toxic agents present in NCP water. anid toxicant present in DD from NCP can directly damage the kidney tubules leading to fibrosis.Item Development and validation of a tool to predict information seeking behaviour of medical undergraduates, Sri Lanka(University of Kelaniya, Sri Lanka, 2022) Marasinghe, M.P.L.R.Information seeking behaviour is a set of actions expressing information needs, searching, evaluating, selecting, and utilizing information. This study aimed to develop and validate a tool to measure the information seeking behaviour of medical undergraduates in Sri Lanka. Final year students and the students, who had completed four years of study in the academic programme in medical faculties in universities of Colombo, Kelaniya, Peradeniya, and Eastern University in Sri Lanka were invited for the study. The elements of information seeking behaviour were defined by thentatically analyzing the content of nine focus group discussions with medical undergraduates of the four faculties. The scale was developed based on the Integrated Behavioural Model. The preliminary scale had 60 items and was pretested. The responses ofa field test with the participation of 436 medical undergraduates were subjected to confirmatory factor analysis (CFA) and psychometric analysis. The tool was refined to include 40 items, and the revised version was administered to 645 medical undergraduates. The 40-item tool supported the good model fit using the absolute fit indices (RMSEA= 0.053, SRMR=0.066). The sub-components of the 40-item tool partially matched with the theoretical framework. The reliability of the entire tool was acceptable (Cronbach’s α = (0.744) and domain levels were in the low to the acceptable range. The internal consistency of the domains; “Intention” (Cronbach’s α = 0.634), “Habit” (Cronbach’s α = 0.561) and “Knowledge & skills” (Cronbach’s α = 0.540) was acceptable in reliability and the domains of “Environmental Constraints” (Cronbach’s α = 0.470) and “Salience” (Cronbach’s α = 0.438) was low in reliability in the 40-item tool. The finalized 40-item tool named ‘Kelaniya Measure of Information Seeking Behaviour’ (KMISB) demonstrated an acceptable level of psychometric rigour in terms of XXV ate reliability and structural validity. KMISB can be used to evaluate and predict information seeking behaviour of medical undergraduates effectively. It facilitates identifying the best practices of information seeking and improving the quality of ae higher education.Item Bionomics and control effects of anopheles stephensi in Mannar and Jaffna districts of Sri Lanka(University of Kelaniya, Sri Lanka, 2023) Jude, P.J.BACKGROUND: Sri Lanka was declared as a country that eliminated malaria disease in 2016 by the World Health Organization. Recent report of Anopheles stephensi as an invasive vector in the northern part of Sri Lanka is one of the challenges to maintain themalaria free states in the country. METHODS: Entomological surveys were conducted at three selected localities in Jaffna and Mannar Districts of Sri Lanka from January 2019 to January 2020 using three entomological techniques. Detailed biology and life cycle related information namely were assessed. Further, effectiveness of insecticide based control efforts (novaluron andtemephos) and application of larvivorous fish Poecilia reticulata were evaluated under laboratory set-up. The Vectorial Capacity (VC) was calculated using a mathematical-based approach. RESULTS: According to the egg morphology, Mysorensis biotype (47%) was the predominant followed by type (38.1%) and intermediate (14.9%). The mating success was 80.7 + 4.45%. The mean hatching period was 1.9 + 0.03 days, with a hatching rate of 86.2 + 0.77%. Overall, 8.0 + 0.14 days were irequired for larval development and 30.3 + 0.14 h were spent in \4e pupal stage. The pupation success was 94.5 + 0.37%, and the majority were males (53.1 + 0.73%). The mean fecundity was 106.5 + 6.38 eggs and a gonotrophic cycle of 3.4 + 0.06 days. The female survival rate was 43.2 + 2.4%, with a mean biting frequency of 66.6 + 3.5%. The average VC of adult An. stephensi was estimated to be 18.7. Significant variations in adult emergence were observed from both larval stages at different salinity levels (P < 0.05). The lowest survival rate was reported as 15.8 2.47% at 25 ppt. The highest mortality rate (100%) at a 1-hour exposure period was observed from temephos at >100 ppm. The nortality rates varied significantly for different concentrations and larvicides (P < 0.05). At 24-h of the exposure period, the 100% mortality of An. stephensi larvae were observed from Bi h temephos and novaluron even at 0.04 ppm. In larvivorous fish study, the survival rate of P. reticulata in both Jaffna and Mannar Districts was significantly different at different chlorine levels (P80% even at 0.75 mg/L. At the 24-hours, the mean survival rates of 70.0+ 5.8% (Jaffna) and 81.7 + 4(Mannar) were observed at 0.75 mg/L. At 48 hours, the fish survived only at 0.75 mg/Lindicating a higher survival rate from Mannar (81.7 + 4.4%), while the fish from Jaffna denoted 70.0 + 5.8% of survival. CONCLUSIONS: The type biotype, which: is an effective vector in the Indian subcontinent is present in Sri Lanka. Anopheles stephensi indicated a vectorial capacity of over 18. There is a high potential of increasing density of An. stephensi in coastal ecosystems. The temephos and novaluron can be recommended as effective larvicides for chemical-based control of An. stephensi in Jaffna, Sri Lanka. The fish captured from Mannar demonstrated a higher tolerance to chlorine levels.Item Activity and bionomic aspects of primary and secondary vectors for dengue transmission in Gampaha district, Sri Lanka(University of Kelaniya, Sri Lanka, 2022) Dalpadado, C.P.R.D.Sri Lanka had experienced periodic dengue epidemics every two to three years for the last two decades. In this scenario, understanding bionomics aspects, and the prevalence of dengue vector species in varied settings will help to develop more accurate and focused vector control approaches. Thus, the current study is intended to elucidate the bionomics of Aedes aegypti and Ae. albopictus, in urban (Negombo, Wattala, Kelaniya), suburban (Attanagalla, Gampaha, Minuwangoda) and rural (Dompe, Meerigama, Divulapitiya) areas of the Gampaha District, Sri Lanka from April 2017 to December 2019. The effectiveness of the insecticide space spraying depends on susceptibility status and the behaviour of the targeted species, hence a part of this study included testing susceptible levels of Ae. aegypti and Ae. albopictus against malathion and deltamethrin insecticides. The study also sought to establish area-specific threshold values for determining the risk of dengue transmission based on larval indices, and a forecasting model for predicting impending dengue outbreaks within the district. Total 19,835 possible breeding habitats were investigated at 13,563 premises where Aedes larvae were identified in 11.03% of premises and 1856 habitats were positive for larvae (Ae. aegypti; 9.8%; Ae. albopictus; 90.2 %). Results showed that Ae. aegypti prefers urban locations while Ae. albopictus is the predominant vector in all spatial settings. Ae. albopictus (54.5%; n= 999) dominated the adult collection, followed by Ae. aegypti (45.5%; n= 835), with a 1:4 male to female ratio. Ae. aegypti mosquitoes demonstrated endophilic resting behaviour, whereas Ae. albopictus were exophilic (Chi-square analysis between the two species; P < 0.001). Resting places of Aedes aegypti recorded as on cloth hangings (36.9%, n=308) and under furniture (40.4%) predominantly in bedrooms (40.4%) and living rooms (24.8%) while Ae. albopictus preferred to rest on outdoor vegetation Xxix 46%(n=460). The majority (43.7 %; n=801) of Aedes mosquitoes rest 1-2 m above ground, and 34.4 % (n=399) rested 1 m or less. The host-seeking cycle of Ae. albopictus was bimodal, with morning peak occurring between 05:00 and 11:00 and afternoon peak between 14:00 and 19:00. While that of Aedes aegypti was with a minor peak between 05:00 and 09:00 and a major peak between 13:00 and 19:00. Physicochemical parameters of mosquito breeding water changed significantly across breeding categories (Kruskal—Willi’s statistics, p < 0.001) showing the change of mosquito susceptibility status. There was a strong positive association between rainfall, larval vector density, and the likelihood of high dengue incidence. When Breteau Index for Ae. aegypti (BIA) exceeds 3.00 and relative humidity exceeds 80%, an early epidemic alert is triggered while BIA > 6.0, case incidence reached an epidemic level in urban areas. In suburban areas, when BI for Ae. albopictus (BIB) > 14.0 an early epidemic alert is triggered. At the BIB > 20, case incidence reached epidemic levels even in absence of Ae. aegypti. Case incidence exceeds the epidermic level in rural areas when the BI for Ae. albopictus is 10 with a one-month latency. In conclusion, area-based entomological thresholds and rational use of insecticides can be proposed for future control of rising dengue epidemics in the Gampaha district based on vector biology/bionomic related evidence through regular monitoring.Item School-based interventions to control dengue vector in the Gampaha district(University of Kelaniya, Sri Lanka, 2022) Radhika, N.M.L.This study was conducted to determine the effectiveness of school-based interventions to control dengue vectors in the Gampaha District, Sri Lanka. Sixty schools were selected randomly from the school registry in four selected educational zones (15 each) as interventional (Kelaniya and Gampaha) and control (Negombo and Minuwangoda). A baseline and three follow-up entomological surveys were conducted in all selected schools at 6-months intervals during 2016-2018. The intervention consisted an activity plan with entomological field surveys, larval control interventions followed by a structured awareness programme of dengue covering general epidemiology, clinical symptoms, prevention, vector control and waste management. Focus group discussions were conducted with stakeholders at 30 intervention schools to identify limitations in current control approaches. The level of awareness of dengue disease was assessed before and after the awareness programme using a structured questionnaire. Awareness levels were categorized as very poor (< 20%), low (21-40%) moderate (41-60%), good (61-80%) and excellent (> 80%). The change in awareness level was determined using General Linear Model. The effectiveness of the vector control interventions were assessed by the total number of dry, water-holding, and infested containers at follow-up survey compared to the baseline. Over, 46.31% (n=1016) of students had good level of awareness prior to the structured awareness programme and reached to the excellent level (41.84%; n=918) after the awareness programme. The improvement of the awareness level was identified as statistically significant according to the chi-square test of independence. At the base-line survey, Aedes albopictus was the predominant species in both control (60%; n=18) and intervention (63.33%; n=19) groups. Leaf axils were the leading breeding habitat followed by discarded plastic and metal containers in the control group. The number of discarded containers was reduced drastically in the interventional schools in the follow-up surveys. There was a statistically significant difference in dry (p<0.001), water-holding (p=0.027), and infested (p=0.006) containers after the last follow-up survey at interventional schools compared to the controls. This study warrants the need of sustainable participation of school community for dengue control. Therefore, strengthening Environmental Pioneer Programme will improve the capacity in dengue control interventions.Item Design, implementation and evaluation of a community intervention to improve utilisation of healthy lifestyle centres in two districts of Sri Lanka(University of Kelaniya, Sri Lanka, 2022) Herath, H.M.T.P.INTRODUCTION: Healthy Lifestyle Centres (HLCs) are underutilised in Sri Lanka. Effectiveness of empowering communities to improve utilisation of HLCs by its target f population (adults aged 35 to 65 years) is not explored. OBJECTIVE: To design, implement and evaluate a community intervention to improve utilisation of HLCs in two districts (Gampaha and Kalutara) of Sri Lanka. METHODS: Phase I, a mixed-methods descriptive study comprising: a qualitative study using grounded theory to explore reasons for the utilisation of HLCs using interviews and a cross-sectional study to assess the profile of users and nonusers and determine associated factors. A multistage cluster sampling method was used to recruit 1727 individuals. Data collected using an interviewer-administered questionnaire were analysed using bivariate and multivariable analysis. Phase II: a quasi-experimental study in six grama niladari divisions each from the catchment areas of two selected HLCs as Intervention (IG) and Comparison Groups (CG). Health Promotion Approach was used to empower Community Support Groups (CSGs) to address underutilisation. Phase III: a pre-post design to evaluate the outcomes. A random sample of 498 from each group was assessed and the primary outcome was the improvement in utilisation (Utilisation of the HLC by a study participant as a first time or as a follow-up client at the time of data collection). RESULTS: The rate of utilisation of the HLCs was 11.3% (n=195, 95% CI:9.80-12.8). HLC utilisation was found to be significantly associated with 14 factors. The factors with highest Odds Ratios (OR) were perceiving screening as useful (OR=10.2, 95% CI: 4.04-23.4) and perceived susceptibility to NCDs (OR= 6.78, 95% CI: 2.79- 16.42). The qualitative study revealed that negative past experiences and attitudes related to staff and services in state health care institutions and HLCs, and employment-related barriers negatively influenced HLC utilisation. The HLC utilisation, which was similar among the IG and CG in the pre assessment (p=0.056), showed a significant improvement in the post assessment (p<0.001). The HLC utilisation in IG increased by 29.5% (pre: 5.85% ; 95% Cl: [3.74-7.95], post: 35.3%; 95% CI: [30.9-39.8]). The CG did not show a significant difference in use. CONCLUSION AND RECOMMENDATIONS: HLC utilisation can be improved through empowering CSGs. The developed intervention model is recommended for use after accounting for contextual differences.Item A Study to assess the improvement of management outcomes in chronic kidney disease of uncertain etiology by introducing clinical pharmacy services to selected out patient renal clinics in the north central province Sri Lanka(University of Kelaniya, Sri Lanka, 2020) Wickramasinghe, N.D.D.OBJECTIVES: To assess impact of “clinic-based pharmacist’ services on drug adherence and health outcomes in stage 4 or 5 pre-dialysis Chronic Kidney Disease of uncertain etiology (CKDu) patients in an out-patient renal clinic in North Central Province, Sri Lanka. METHODOLOGY: A randomized controlled clinical trial was conducted in Teaching Hospital, Anuradhapura. Demography, drug adherence (using BMQ Score), management outcomes, and Quality of Life (using KDQOL-SF™) were assessed. Intervention(I) group received four counseling sessions by a “clinic-based pharmacist” plus usual clinic care over 12 months. Control (C) group received usual care. RESULTS: Of 256 eligible patients, 127 were allocated to C and 129 to I. Demography and baseline outcome measures were similar. At 12 months, median BMQ scores improved from 5(3-5) to 3(2-4) (p<0.050), mean hemoglobin (Hb) levels improved from 11.02±1.44g/dL to 11.41±1.37g/dL (p<0.050) and QOL improved in I group. In C group, mean diastolic blood pressure and mean serum creatinine increased and eGFR was reduced, but those outcomes were unaltered in I group. CONCLUSION: “Clinic-based pharmacist” services improved drug adherence, Hb levels and QOL in stage 4 or 5 pre-dialysis CKDu patients. This service can improve disease outcomes.Item Perception knowledge and attitudes on use of banned substances in sports among junior athletes and coaches in Sri Lanka and development of a learning module to address them through the school curriculum(University of Kelaniya, Sri Lanka, 2021) Kumari, M.I.P.INTRODUCTION: Use of banned substances in sports to improve training and performance is an unethical practice. OBJECTIVE: To explore the perceptions and describe the knowledge and attitudes of. junior athletes and coaches on the use of banned substances in sports and to develop a learning module for students of Grades 9 and 10 to address gaps in knowledge and attitudes regarding the use of banned substances in sports. METHODS: This study comprises a qualitative study, a descriptive cross-sectional study, -and the development of an outcome based learning module. Junior athletes and ' coaches of ten sports representing the three best performing schools in each sport participated. Qualitative data were collected from twenty athletes and ten coaches using interviews and thematically analysed using NVivo (version12). In the cross- - sectional study, data were collected from 552 athletes and 30 coaches using a pretested self-administered questionnaire and analysed using SPSS Version 21 and presented using frequency distributions. All data were collected after informed written consent of the participants and parents when the participants were under-age. The findings were presented to a panel of experts in sports science, public health and education. Based on expert opinion and theories of outcome based education, a learning module was developed and was reviewed by an independent panel of educational and sports science experts and improved before finalization. RESULTS: Most of the athletes and coaches perceive that they have limited knowledge of banned substances in sports which should be improved. They perceive that the use of banned substances in sports is unacceptable. Only 79% of athletes have heard the term ‘doping’ Athletes engaged in athletics, weightlifting, rugby and badminton have a better level of knowledge. Only 56.7% of coaches report that they regularly update their knowledge. Coaches and athletes identified the school curriculum as the most effective mode to impart knowledge on this topic, followed by digital and print media. The newly developed learning module incorporates traditional and modern pedagogy to deliver content and use assessment methods aligned to learning outcomes. DISCUSSION: There is a clear need to educate school children and coaches about banned substances in sports. School curriculum is recognized as the most effective mode of delivery. The learning module delivered in grades 9 and 10 will be helpful to bridge the current gap in knowledge and attitudes.