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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty

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    Comparison of four low-cost carbapenemase detection tests and a proposal of an algorithm for early detection of carbapenemase-producing Enterobacteriaceae in resource-limited settings
    (Public Library of Science, 2021) Kumudunie, W.G.M.; Wijesooriya, L.I.; Wijayasinghe, Y.S.
    ABSTRACT: Rapidly progressing antibiotic resistance is a great challenge in therapy. In particular, the infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are exceedingly difficult to treat. Carbapenemase production is the predominant mechanism of resistance in CRE. Early and accurate identification of carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) is extremely important for the treatment and prevention of such infections. In the present study, four phenotypic carbapenemase detection tests were compared and an algorithm was developed for rapid and cost-effective identification of CP-CRE. A total of 117 Enterobacteriaceae (54 CP-CRE, 3 non-CP-CRE, and 60 non-CRE) isolates were tested for carbapenemase production using modified Hodge test (MHT), modified carbapenem inactivation method (mCIM), Carba NP test (CNPt), and CNPt-direct test. The overall sensitivity/specificity values were 90.7%/92.1% for MHT, 100%/100% for mCIM, 75.9%/100% for CNPt, and 83.3%/100% for CNPt-direct. OXA-48-like enzymes were detected with 93.2% sensitivity by MHT and >77.3% sensitivity by two Carba NP tests. MHT could only detect half of the NDM carbapenemase producers. CNPt-direct exhibited enhanced sensitivity compared to CNPt (100% vs 25%) for detection of NDM producers. Considering these findings we propose CNPt-direct as the first test followed by mCIM for rapid detection of CP-CRE. With this algorithm >80% of the CP-CRE could be detected within 24 hours from the time the sample is received and 100% CP-CRE could be detected in day two. In conclusion, mCIM was the most sensitive assay for the identification of CP-CRE. CNPt-direct performed better than CNPt. An algorithm consisting CNPt-direct and mCIM allows rapid and reliable detection of carbapenemase production in resource-limited settings.
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    Prediction of colorectal cancer risk among adults in a lower middle-income country
    (AME Publishing Company, 2019) Samarakoon, Y.M.; Gunawardena, N.S.; Pathirana, A.; Perera, M.N.; Hewage, S.A.
    BACKGROUND: Globally, colorectal cancer (CRC) is ranked as the third most common cancer in men and the second in women. Use of a simple, validated risk prediction tool will offer a low-cost mechanism to identify the high-risk individuals for CRC. This will increase efficient use of limited resources and early identification of patients. The aim of our study was to develop and validate a risk prediction model for developing CRC for Sri Lankan adults. METHODS: The risk predictors were based on the risk factors identified through a logistic regression model along with expert opinion. A case control design utilizing 65 CRC new cases and 65 hospital controls aged 30 years or more was used to assess the criterion validity and reliability of the model. The information was obtained using an interviewer administered questionnaire based on the risk prediction model. RESULTS: The developed model consisted of eight predictors with an area under the curve (AUC) of 0.849 (95% CI: 0.8 to 0.9, P<0.001). It has a sensitivity of 76.9%, specificity of 83.1%, positive predictive value (PPV) of 82.0%, negative predictive value (NPV) of 79.3%. Positive and negative likelihood ratios are 4.6 and 0.3. Test re-test reliability revealed a Kappa coefficient of 0.88. CONCLUSIONS: The model developed to predict the risk of CRC among adults aged 30 years and above was proven to be valid and reliable and it is an effective tool to be used as the first step to identify the high-risk population who should be referred for colonoscopy examination. © Journal of Gastrointestinal Oncology. All rights reserved.
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    Antibiotic sensitivity patterns among extended spectrum β-lactamase (ESBL) producing organisms causing urinary tract infections in Sri Lanka
    (Sri Lanka Medical Association, 2016) Luke, W.A.N.V.; Fernando, S.C.; Wickremasinghe, R.D.S.S.; Sebastiampillai, B.S.; Gunathilake, M.P.M.L.; Miththinda, J.K.N.D.; Silva, F.H.D.S.; Premaratna, B.A.H.R.
    INTRODUCTION AND OBJECTIVES: ESBLs are enzymes that confer resistance to all penicillins, cephalosporins, and aztreonam. ESBL producing organisms causing urinary tract infections (ESBL-UTI) are increasing in incidence and pose a major burden to health care requiring treatment with expensive antimicrobials and prolonged hospital stay. Documented antibiotic susceptibility of ESBL organisms include meropenem (95-100%) and aminoglycosides (45-60%). This study evaluated the antibiotic sensitivity patterns of ESBL-UTI in Sri Lanka. METHOD: Patients with ESBL-UTI admitted to Professorial Medical Unit, Colombo North Teaching Hospital (CNTH) from January – June 2015 were recruited to the study. Their Urine culture and ABST reports were evaluated after obtaining informed written consent. RESULTS: Of 61 culture positive ESBL-UTIs, E. coli accounted for 53 (86.8%), followed by Klebsiella in the 8 (13.1%). The ESBL organisms were mostly sensitive to carbapenems; 58 (95%) to Meropenem and 45 (73.7%) to Imipenem. The other sensitivity patterns were 37 (60.6%) to Amikacin, and 28 (45.9%) to Nitrofurantoin. Meropenem resistance was observed in 3 (4.9%) and were E.coli. These three patients had received multiple antibiotics including meropenem in the recent past for recurrent UTI. CONCLUSIONS: It is evident from the above data that Carbapenems remain as the first line therapy for the majority of ESBL-UTI in the local setting. However 4.9 % prevalence of meropenem resistance is alarming compared to 0.4% prevalence in Pakistan and 0.02% prevalence in Germany. Such high prevalence of meropenem resistance should draw attention of clinicians and needs to implement measures to prevent emergence and spread of carbapenum resistant ESBL organisms in the country.
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    A Diagnostic scoring model for Leptospirosis in resource limited settings
    (Public Library of Science, 2016) Rajapakse, S.; Weeratunga, P.; Niloofa, R.; Fernando, N.; de Silva, N.L.; Rodrigo, C.; Maduranga, S.; Nandasiri, N.; Premawansa, S.; Karunanayake, L.; de Silva, H.J.; Handunnetti, S.
    Leptospirosis is a zoonotic infection with significant morbidity and mortality. The clinical presentation of leptospirosis is known to mimic the clinical profile of other prevalent tropical fevers. Laboratory confirmation of leptospirosis is based on the reference standard microscopic agglutination test (MAT), direct demonstration of the organism, and isolation by culture and DNA detection by polymerase chain reaction (PCR) amplification. However these methods of confirmation are not widely available in resource limited settings where the infection is prevalent, and reliance is placed on clinical features for provisional diagnosis. In this prospective study, we attempted to develop a model for diagnosis of leptospirosis, based on clinical features and standard laboratory test results. METHODS: The diagnostic score was developed based on data from a prospective multicentre study in two hospitals in the Western Province of Sri Lanka. All patients presenting to these hospitals with a suspected diagnosis of leptospirosis, based on the WHO surveillance criteria, were recruited. Confirmed disease was defined as positive genus specific MAT (Leptospira biflexa). A derivation cohort and a validation cohort were randomly selected from available data. Clinical and laboratory manifestations associated with confirmed leptospirosis in the derivation cohort were selected for construction of a multivariate regression model with correlation matrices, and adjusted odds ratios were extracted for significant variables. The odds ratios thus derived were subsequently utilized in the criteria model, and sensitivity and specificity examined with ROC curves. RESULTS: A total of 592 patients were included in the final analysis with 450 (180 confirmed leptospirosis) in the derivation cohort and 142 (52 confirmed leptospirosis) in the validation cohort. The variables in the final model were: history of exposure to a possible source of leptospirosis(adjusted OR = 2.827; 95% CI = 1.517-5.435; p = 0.001) serum creatinine > 150 micromol/l (adjusted OR = 2.735; 95% CI = 1.374-4.901; p = 0.001), neutrophil differential percentage > 80.0% of total white blood cell count (adjusted OR 2.163; 95% CI = 1.309-3.847; p = 0.032), serum bilirubin > 30 micromol/l (adjusted OR = 1.717; 95% CI 0.938-3.456; p = 0.049) and platelet count < 85,000/mm3 (adjusted OR = 2.350; 95% CI = 1.481-4.513; p = 0.006). Hosmer-Lemeshow test for goodness of fit was 0.931. The Nagelkerke R2 was 0.622. The area under the curve (AUC) was noted as 0.762. A score value of 14 reflected a sensitivity of 0.803, specificity of 0.602, a PPV of 0.54, NPV of 0.84, a positive LR of 2.01 and a negative LR of 0.32. CONCLUSIONS: The above diagnostic model for diagnosis of leptospirosis is suggested for use in clinical settings. It should be further validated in clinical practice.
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    Sensitive and inexpensive molecular test for falciparum malaria: detecting Plasmodium falciparum DNA directly from heat-treated blood by loop-mediated isothermal amplification
    (American Association For Clinical Chemistry, 2006) Poon, L.; Wong, B.W.; Ma, E.H.; Chan, K.H.; Chow, L.M.; Abeyewickreme, W.; Tangpukdee, N.; Yuen, K.Y.; Guan, Y.; Looareesuwan, S.; Peiris, J.S.
    BACKGROUND: Malaria is one of the most important parasitic infections in humans. A sensitive diagnostic test for malaria that could be applied at the community level could be useful in programs to control the disease. The aim of the present work was to develop a simple, inexpensive moleculartest for Plasmodium falciparum. METHODS: Blood was collected from controls (n = 100) and from patients diagnosed with falciparum malaria infection (n = 102), who were recruited to the study. Heat-treated blood samples were tested by a loop-mediated isothermal amplification (LAMP) assay for P. falciparum. Results were interpreted by a turbidity meter in real time or visually at the end of the assay. To evaluate the assay, DNA from these samples was purified and tested by PCR. Results from the LAMP and PCR assays were compared. RESULTS: The LAMP assay detected P. falciparum directly from heat-treated blood. The quantitative data from the assay correlated to the parasite counts obtained by blood-film microscopic analyses. When we used the PCR assay as the comparison method, the sensitivity and specificity of the LAMP assay were 95% and 99%, respectively. CONCLUSIONS: Unlike PCR, the LAMP assay does not require purified DNA for efficient DNA amplification, thereby reducing the cost and turnaround time for P. falciparum diagnosis. The assay requires only basic instruments, and assay positivity can be verified by visual inspection
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    Identifying the biting species in snakebite by clinical features: an epidemiological tool for community surveys
    (Oxford University Press, 2006) Pathmeswaran, A.; Kasturiratne, A.; Fonseka, M.; Nandasena, S.; Lalloo, D.G.; de Silva, H.J.
    The outcome of snakebite is related to the biting species but it is often difficult to identify the biting snake, particularly in community settings. We have developed a clinical scoring system suitable for use in epidemiological surveys, with the main aim of identifying the presumed biting species in those with systemic envenoming who require treatment. The score took into account ten features relating to bites of the five medically important snakes in Sri Lanka, and an algorithm was developed applying different weightings for each feature for different species. A systematically developed artificial data set was used to fine tune the score and to develop criteria for definitive identification. The score was prospectively validated using 134 species-confirmed snakebites. It correctly differentiated the bites caused by the three snakes that commonly cause major clinical problems (Russell's viper (RV), kraits and cobra) from other snakes (hump-nosed viper (HNV) and saw-scaled viper (SSV)) with 80% sensitivity and 100% specificity. For individual species, sensitivity and specificity were, respectively: cobra 76%, 99%; kraits 85%, 99%; and RV 70%, 99%. As anticipated, the score was insensitive in the identification of bites due to HNV and SSV
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