Browsing by Author "Luke, N."
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Item Antibiotic sensitivity patterns among ESBL UTIs in Sri Lanka(Elsevier, 2016) Luke, N.; Wickramasinghe, B.; Sebastiampillai, M.; Miththinda, N.; Fernando, S.; Silva, S.; Premaratna, R.BACKGROUND: Extended-spectrum β-lactamase (ESBL) producing organisms causing urinary tract infections (UTI) are increasing in incidence and poses a major burden to health care requiring treatment with expensive antimicrobials and prolonged hospital stay. The prevalence of ESBL producing organisms particularly in the Asian region remains unknown. In a study carried out in a tertiary care center in India,70/218(32.1%) clinical isolates of Enterobacteriaceae were confirmed as ESBL. Of them K. pneumonia were the most common ESBL producers(46.4%), followed by E coli (31.7%). Previous studies to evaluate antibiotic susceptibility shows high sensitivity to meropenem (95-100%) with aminoglycoside susceptibility ranging from 45-60%. Objective of this study was to evaluate the antibiotic sensitivity patterns of ESBL UTIs in Sri Lanka. METHODS & MATERIALS: Patients with ESBL-UTI admitted to Professorial Medical Unit, Colombo North Teaching Hospital, Ragama over a period of 6 months from January-July 2015 were recruited to the study. Their Urine culture and ABST reports were analysed after obtaining informed written consent. RESULTS: There were 52 patientswho consented for the study;males30 (57.7%),mean (SD) age 64.11 (12.59)years. The most common organisms causing the ESBL-UTI were E. coli in 44(84.6%),followed by Klebsiella in 8 (15.4%) . The ESBL organisms were mostly sensitive to carbapenems;Meropenem 50 (96.2%) and Imipenem in 38(73.1%). The other sensitivity patterns were Amikacin in 30 (57.7%), Nitrofurantoin in 24 (46.2%) andCeftriaxone in 2 (3.8%). None were sensitive to Ceftazidime. Meropenem resistance was found in 2 (3.8%) and wereE.coli. These two patients had received multiple antibiotics including meropenem in the recent past for recurrant UTI.CONCLUSION: It is evident from the above data that Carbapenems remain as the first line therapy for the majority of UTIs caused by ESBL producing organisms in the local setting. However 3.8% prevalence of meropenem resistance among the study population should draw attention of clinicians and needs implementation of measures to prevent emergence and spread of carbapenum resistant ESBL organisms.Item Attitudes of nurses in palliative care – A Sri Lankan study(Sri Lanka Medical Association, 2016) Silva, F.H.D.S.; Luke, N.; Piyarathne, S.P.M.L.R.; de Silva, S.T.INTRODUCTION AND OBJECTIVES: Care of terminally ill patients and their families by health care workers (HCW) is variable from person to person. The quality of care is influenced by attitudes that the provider holds towards the concept of palliation. There is no formal education or training of HCW in Sri Lanka. This study aimed to determine the attitudes of nurses towards the dying process of a patient in the context of palliative care. METHOD: Nurses working in general medical and surgical wards and critical care units at the Colombo North Teaching Hospital, Ragama were assessed with the Frommelt Attitudes Towards Care of the Dying (FATCOD) scale (a 30 item, 5 point Likert Scale) using a self administered questionnaire. A total of 105 volunteers (general ward – 53, critical care- 52) participated in this study. RESULTS: The total FATCOD score for nurses in general wards was 107.51 (+/- 12.3) while it was 110.64 (+/-15.4) for critical care nurses (range 30-150). The mean FATCOD score for nurses in general wards was 3.58 (+/- 0.49) while nurses in critical care units achieved 3.68 (+/- 0.52). There were no significant differences of the mean scores with regards to nursing grade or duration of service (p<0.05). Scores related to communication between nurses and patients/carers were observed to be low along with the score on family interference in patient care. CONCLUSIONS: The results of this study demonstrate lower scores in all questions when compared to studies done in developed countries. The importance of developing strategies to improve delivery of palliative care services is paramount.Item Characteristics and survival of advanced untreated hepatocellular carcinoma of non-viral etiology(Indian Society of Gastroenterology, 2024) Ekanayaka, S.P.N.; Luke, N.; Thilakarathne, S.B.; Dassanayake, A.; Gunetilleke, M.B.; Niriella, M.A.; Siriwardana, R.C.INTRODUCTION AND OBJECTIVES Hepatocellular carcinoma (HCC) is an aggressive tumor and presents late. The underlying etiology of HCC is changing rapidly. HCC in Sri Lanka is unique due to its predominant non-viral etiology (nvHCC) but lacks survival data.METHOD Data was collected from patients who presented with HCC from 2011 to 2018. There were 560/568 (98.6%) nvHCC. The patients who were not candidates for tumor-specific treatment (149/560 [26.7%]) were selected. Population characteristics, demographic data, tumor characteristics, survival and factors affecting survival were analyzed.RESULTS The median age was 64 years (range 30-88) and 86% (n = 129) were males. As many as 124 (83%) were cirrhotic. The overall performance score was 80%. Nearly 21/124 tumors were detected in cirrhotic screening. Tumors were single nodular in 32 (21%), up to three nodules in 28 (18%), more than three nodules in 33 (22%) and diffusely infiltrating in 56 (37%). The major venous invasions were present in 78 (52.3%). Extra-hepatic tumor spread was seen in 19 (12.7%) (lungs 13 [72.2%], bones 2 [11.1%]). The median survival of patients receiving palliative care was three months (1-43 months). Tumor size and cirrhotic status were significant predictors in univariate analysis.CONCLUSION A quarter of nvHCCs were not amenable to treatment at presentation as they had dismal survival.Item Determinants of uncontrolled hypertension in rural communities in South Asia - Bangladesh, Pakistan, and Sri Lanka(Oxford University Press, 2018) Jafar, T.H.; Gandhi, M.; Jehan, I.; Naheed, A.; de Silva, H.A.; Shahab, H.; Alam, D.; Luke, N.; Lim, C.W.; COBRA-BPS Study GroupBACKGROUND: Uncontrolled blood pressure (BP) is a leading risk factor for death and disability in South Asia. We aimed to determine the cross-country variation, and the factors associated with uncontrolled BP among adults treated for hypertension in rural South Asia. METHODS: We enrolled 1718 individuals aged ≥40 years treated for hypertension in a cross-sectional study from rural communities in Bangladesh, Pakistan, and Sri Lanka. Multivariable logistic regression model was used to determine the factors associated with uncontrolled BP (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg). RESULTS: Among hypertensive individuals, 58.0% (95% confidence interval 55.7, 60.4) had uncontrolled BP: 52.8% (49.0, 56.6) in Bangladesh, 70.6% (65.7, 75.1) in Pakistan, and 56.5% (52.7, 60.1) in Sri Lanka. The odds (odds ratio (95% confidence interval)) of uncontrolled BP were significantly higher in individuals with lower wealth index (1.17 (1.02, 1.35)); single vs married (1.46 (1.10, 1.93)); higher log urine albumin-to-creatinine ratio (1.41 (1.24, 1.60)); lower estimated glomerular filtration rate (1.23 (1.01, 1.49)); low vs high adherence to antihypertensive medication (1.50 (1.16, 1.94)); and Pakistan (2.91 (1.60, 5.28)) vs Sri Lanka. However, the odds were lower in those with vs without self-reported kidney disease (0.51 (0.28, 0.91)); and receiving vs not receiving statins (0.62 (0.44, 0.87)). CONCLUSIONS: The majority of individuals with treated hypertension have uncontrolled BP in rural Bangladesh, Pakistan, and Sri Lanka with significant disparities among and within countries. Urgent public health efforts are needed to improve access and adherence to antihypertensive medications in disadvantaged populations in rural South Asia.Item Factors associated with urinary tract infections caused by extended spectrum beta-lactamase (ESBL) producing organisms in Sri Lanka(Elsevier, 2016) Fernando, S.; Luke, N.; Wickramasinghe, S.; Sebastiampillai, B.; Gunathilake, M.; Miththinda, N.; Silva, S.; Premaratna, R.BACKGROUND: Urinary tract infections (UTI) caused by extendedspectrum beta-lactamase (ESBL)-producing organisms are a major burden in clinical practice. Hospitalization in the past 3 months, antibiotic treatment in the past 3 months, age over 60 years, diabetes mellitus, Klebsiella pneumoniae infection, previous use of second or third-generation cephalosporins, quinolones or penicillins are known associations and risk factors for ESBL-UTI. METHODS & MATERIALS: A descriptive study was conducted over a period of 6 months from January - July 2015 recruiting patients with UTI caused by ESBL producing organisms, who were admitted to the Professorial Medical unit, Colombo North Teaching Hospital, Ragama Sri Lanka in order to identify risk factors and associations. Data were obtained using a pre-tested interviewer administered questionnaire and from relevant medical records after obtaining informed written consent. RESULTS: 52 patients were recruited; males 30 (57.7%), mean (SD) age 64.1(.12.6)years. Of them, 46 (88.5%) had diabetes mellitus, 32 (61.5%) had hypertension and 10 (19.2%) had chronic liver disease as comorbidities.20 (38.5%) had ultrasonographic evidence of acute pyelonephritis. At presentation16 (30.8%)had biochemical and/or ultrasonographic evidence of chronic or acute on chronic kidney disease. History of constipation was observed in 18 (34.6%), hospitalization during the past 3 months was seen in 24(46.2%)and history of urinary catheterization in 16(30.8%). Features of obstructive uropathy such as hydronephrosis, hydroureter and prostatomegaly were seen in 4 (7.7%) patients each. Antibiotic treatment within the past 3 months was observed in 32(61.5%);penicillins in 18(34.6%), 3rd generation cephalosporins in 16(30.8%),quinolones in 14(26.9%) and 2nd generation cehalosporins in 12 (23.1%). 18 (34.6%) had received more than one antibiotic within the past 3 months. 8(15.4%)patients studied were on prophylactic antibiotics for recurrant UTIs. None of them had recent Klebsiella pneumonia. CONCLUSION: Similar to other studies,diabetes mellitus, recent antibiotic treatment, hospitalization and catheterization were observed in our patients with ESBL-UTI. The fact that only 53.8% patients had received antibiotics at community level and 38.5% patients had never received antibiotics prior to developing ESBLUTI suggest high prevalence of ESBL producing organisms at community level.Item Factors associated with Urinary tract infections caused by extended spectrum β-lactamase (ESBL) producing organisms in Sri Lanka(Elsevier, 2016) Fernando, S.; Luke, N.; Wickramasinghe, S.; Sebastiampillai, B.; Gunathilake, M.; Miththinda, N.; Silva, S.; Premaratna, R.BACKGROUND: Urinary tract infections (UTI) caused by extended-spectrum β-lactamase (ESBL)-producing organisms are a major burden in clinical practice. Hospitalization in the past 3 months, antibiotic treatment in the past 3 months, age over 60 years, diabetes mellitus, Klebsiella pneumoniae infection, previous use of second or third-generation cephalosporins, quinolones or penicillins are known associations and risk factors for ESBL-UTI. METHODS & MATERIALS: A descriptive study was conducted over a period of 6 months from January - July 2015 recruiting patients with UTI caused by ESBL producing organisms, who were admitted to the Professorial Medical unit, Colombo North Teaching Hospital, Ragama Sri Lanka in order to identify risk factors and associations. Data were obtained using a pre-tested interviewer administered questionnaire and from relevant medical records after obtaining informed written consent. RESULTS: 52 patients were recruited; males 30 (57.7%), mean (SD) age 64.1(.12.6)years. Of them, 46 (88.5%) had diabetes mellitus, 32 (61.5%) had hypertension and 10 (19.2%) had chronic liver disease as comorbidities.20 (38.5%) had ultrasonographic evidence of acute pyelonephritis. At presentation16 (30.8%)had biochemical and/or ultrasonographic evidence of chronic or acute on chronic kidney disease. History of constipation was observed in 18 (34.6%), hospitalization during the past 3 months was seen in 24(46.2%)and history of urinary catheterization in 16(30.8%). Features of obstructive uropathy such as hydronephrosis, hydroureter and prostatomegaly were seen in 4 (7.7%) patients each. Antibiotic treatment within the past 3 months was observed in 32(61.5%);penicillins in 18(34.6%), 3rd generation cephalosporins in 16(30.8%),quinolones in 14(26.9%) and 2nd generation cehalosporins in 12 (23.1%). 18 (34.6%) had received more than one antibiotic within the past 3 months. 8(15.4%)patients studied were on prophylactic antibiotics for recurrant UTIs. None of them had recent Klebsiella pneumonia. CONCLUSION: Similar to other studies,diabetes mellitus, recent antibiotic treatment, hospitalization and catheterization were observed in our patients with ESBL-UTI. The fact thatonly 53.8% patients had received antibiotics at community level and 38.5% patients had never received antibiotics prior to developing ESBL-UTIsuggest high prevalence of ESBL producing organisms at community level.Item Glycaemic control and avenues for improvement among people with type 2 diabetes mellitus from rural Sri Lanka – a retrospective cohort study(Elsevier, 2023) Mettananda, C.; Chathuranga, U.; Rathnayake, T.; Luke, N.; Meegodavidanage, N.BACKGROUND The majority of Sri Lankans and South Asians are rural dwellers but follow-up data on glycaemic control and its associations in rural communities are sparse. We followed up a cohort of hospital-based rural Sri Lankans with diabetes from diagnosis up to 24-months. METHODS We conducted a retrospective cohort study of people with type-2 diabetes (T2DM) diagnosed 24 months before enrolment who were being followed up at Medical/Endocrine clinics of five hospitals selected by stratified random sampling in Anuradhapura, a rural district of Sri Lanka from June 2018 to May 2019 and retrospectively followed them up to the diagnosis of the disease. Prescription practices, cardiovascular risk factor control and their correlates were studied using self-administered and interviewer-administered questionnaires and perusing medical records. Data were analysed using SPSS version-22. FINDINGS A total of 421 participants [mean age 58.3 ± 10.4 years, female 340 (80.8%)] were included in the study. Most participants were started on anti-diabetic medications in addition to lifestyle measures. Of them, 270 (64.1%) admitted poor dietary-control, 254 (60.3%) inadequate medication-compliance and 227 (53.9%) physical inactivity. Glycaemic control was assessed mainly on fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) data were available in only 44 (10.4%). Target achievements in FPG, blood pressure, body mass index and non-smoking at 24-months following initiation of treatment were 231/421 (54.9%), 262/365 (71.7%), 74/421 (17.6%) and 396/421 (94.1%) respectively. INTERPRETATION In this cohort of rural Sri Lankans with type-2 diabetes mellitus, all were started on anti-diabetic medications at the diagnosis, but glycaemic target achievement was inadequate at 24 months. We identified the major patient-related reasons for poor blood glucose control were poor compliance with diet/lifestyle and/or medications and misconceptions about antidiabetic medications.Item Identification of patients with type 2 diabetes with non-alcoholic fatty liver disease who are at increased risk of progressing to advanced fibrosis: a cross-sectional study(BMJ Publishing Group Ltd, 2023) Mettananda, C.; Egodage, T.; Dantanarayana, C.; Fernando, R.; Ranaweera, L.; Luke, N.; Ranawaka, C.; Kottahachchi, D.; Pathmeswaran, A.; de Silva, H.J.; Dassanayake, A.S.INTRODUCTION: Identification of advanced hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD) is important as this may progress to cirrhosis and hepatocellular carcinoma. The risk of hepatic fibrosis is especially high among patients with diabetes with NAFLD. Annual screening of patients with diabetes for fatty liver and calculation of Fibrosis-4 (FIB-4) score and exclusion of significant fibrosis with vibration-controlled transient elastography (VCTE) have been recommended. However, VCTE is expensive and may not be freely available in resource-limited settings. We aim to identify predictors of significant liver fibrosis who are at increased risk of progression to advanced liver fibrosis and to develop a prediction model to prioritise referral of patients with diabetes and NAFLD for VCTE. METHODS AND ANALYSIS: This cross-sectional study is conducted among all consenting adults with type 2 diabetes mellitus with NAFLD at the Colombo North Teaching Hospital, Ragama, Sri Lanka. All patients get the FIB-4 score calculated. Those with FIB-4 ≥1.3 undergo VCTE (with FibroScan by Echosens). Risk associations for progression to advanced liver fibrosis/cirrhosis will be identified by comparing patients with significant fibrosis (liver stiffness measure (LSM) ≥8 kPa) and without significant fibrosis (LSM <8 kPa). A model to predict significant liver fibrosis will be developed using logistic regression. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (P/66/07/2021). Results of the study will be disseminated as scientific publications in reputable journals.Item Regional Variation in Comorbid Prediabetes and Diabetes and Associated Factors among Hypertensive Individuals in Rural Bangladesh, Pakistan, and Sri Lanka(Hindawi Publishing Corporation, 2019) Feng, L.; Naheed, A.; de Silva, H.A.; Jehan, I.; Raqib, R.; Islam, M.T.; Luke, N.; Kasturiratne, A.; Farazdaq, H.; Senan, S.; Jafar, T.H.; Cobra-Bps Study GroupWe aimed to explore the cross-country variation in the prevalence of comorbid prediabetes or diabetes and determine the sociodemographic, lifestyle, and clinical factors, especially body mass index (BMI) and waist circumference, associated with comorbid diabetes in individuals with hypertension in rural South Asia. We analyzed cross-sectional data of 2426 hypertensive individuals of ≥40 years from 30 randomly selected rural communities in Bangladesh, Pakistan, and Sri Lanka. Prediabetes was defined as fasting plasma glucose (FPG) between 100 and 125 mg/dL without use of antidiabetic treatment and diabetes as FPG ≥126 mg/dL or use of antidiabetic medication. The prevalence (95% CI) of prediabetes or diabetes (53.5% (51.5%, 55.5%)) and diabetes (27.7% (25.9%, 29.5%)) was high in the overall hypertensive study population in rural communities in 3 countries. Rural communities in Sri Lanka had the highest crude prevalence of prediabetes or diabetes and diabetes (73.1% and 39.3%) with hypertension, followed by those in Bangladesh (47.4% and 23.1%) and Pakistan (39.2% and 20.5%). The factors independently associated with comorbid diabetes and hypertension were residing in rural communities in Sri Lanka, higher education, international wealth index, waist circumference, pulse pressure, triglyceride, and lower high-density lipoprotein. The association of diabetes with waist circumference was stronger than with BMI in hypertensive individuals. Prediabetes or diabetes are alarmingly common among adults with hypertension and vary among countries in rural South Asia. The high prevalence of comorbid diabetes in Sri Lanka among hypertensives is not fully explained by conventional risk factors and needs further etiological research. Urgent public health efforts are needed to integrate diabetes control within hypertension management programs in rural South Asia, including screening waist circumference.Item Sero-prevalence of rickettsial infections in patients with Parkinson’s disease(Sri Lanka Medical Association, 2017) Gunathilake, M.P.M.L.; Luke, N.; Benedict, S.; Wickremasinghe, S.; Ranawaka, U.K.; Premaratna, R.INTRODUCTION & OBJECTIVES: Role of infections in Parkinson’s disease (PD) pathogenesis has been proposed. A patient who had features of PD during scrub typhus infection fully recovered following treatment. Two years later, he developed features suggestive of early PD and raised the question, whether rickettsial infections could trigger development of PD. METHODS: In order to study the sero-prevalence of rickettsioses, a descriptive cross-sectional study was carried out in patients with diagnosed PD. Their IFA-IgG titres against O. tsutsugamushi (IFA-IgG-OT) antigens at 1:32 and 1:128 dilutions were compared with the population seroprevalence. Statistical analysis was performed using SPSS. RESULTS: A total of 35 patients; 20 (57.1%) males [mean age 62 years (SD 8.8)], 15 (42.9%) females [mean age 68.5 years (SD 7.4)]. Mean age at diagnosis of PD; males: 57.2 years (SD 9.7), females: 64.7 years (7.5). 10/35 (29.8%) had IFA-IgG-OT titre 1:32 (p=0.19 compared to population sero-prevalence of 19.8%) and one had a titre 1:128 (2.8% compared to population prevalence of 3.17%). At the time of assessment for sero-prevalence of rickettsioses, the mean (SD) duration of diagnosis of PD between IFA-IgG +ve vs IFA-IgG –ve were 4.3(3.9) vs 4.2(4.4) years. CONCLUSION: Although patients with PD had a higher percentage sero-prevalence compared to the population, it was not significantly different. The drawback of this study was the long duration of PD at the time IFA-IgG levels were done. Following up of patients who present with extrapyramidal features due to acute rickettsioses and assessing whether they later develop PD would help to arrive at conclusions.Item Sporadic cases of adult measles: a research article(BioMed Central, 2017) Premaratna, R.; Luke, N.; Perera, H.; Gunathilake, M.; Amarasena, P.; Chandrasena, T.G.A.N.BACKGROUND: Measles caused by a paramyxovirus, characterized by fever, malaise, cough, coryza conjunctivitis, a maculopapular rash is known to result in pneumonia, encephalitis and death. Fatal cases of measles in Sri Lanka are rare after implementation of the National Immunization Programme in 1984. Thereafter 0.1% case fatality rate was observed during October 1999-June 2000 which is a very low figure compared to other regional countries. Immunization guidelines were further revised in 2001, 2011 and in 2012 when additional immunization was recommended to age group 4-21 years; who are likely to have inadequate immunization, in order to achieve elimination of Measles by 2020. However, in 2013-2014, 4690 cases were reported and the majority were children less than 1 year of age. The occurrence in adults is hard to retrieve in published epidemiological reports, however had been 38% (out of 1008 patients) in the 3rd quarter of 2013. During this outbreak 73/101 (72%) reported from the North Central Province of Sri Lanka had been more than 12 years of age with 50% being more than 29 years. 14 Sri lankan adult patients [median age 32 years (range 25-48)] who presented sporadically from June 2014 to March 2016, with confirmed measles infection were enrolled retrospectively after informed consent. Details with regards to their clinical presentation, immunization and other relevant areas were collected using an interviewer administered questionnaire or using patient management records. RESULTS: The patients presented with high fever, headache, severe body aches, sore throat, dry cough, intense tearing, red eyes and posterior cervical lymphadenopathy over 3-5 days duration. Later they developed discrete maculopapular rash helping the diagnosis. They had a variable degree of leucopenia, lymphocytosis, thrombocytopenia and derangements in the liver functions mimicking any other acute febrile illnesses such as dengue, chikungunya, leptospirosis or Zika virus infection. CONCLUSION: At least a 3-5 day delay in the diagnosis was observed (even after the appearance of the rash in some patients), due to non-awareness of its occurrence, unfamiliarity of measles in adults, non-specific nature of the illness and non-availability of rapid diagnostics, risking transmission to the immune-compromised or non-immune staff or patients. Identification of the source of infection in these sporadic adult cases and their virologic surveillance and molecular epidemiology will be important to interrupt the transmission and to achieve the targeted elimination of measles from Sri Lanka by 2020.Item Widespread subcutaneous necrosis in spotted fever group Rickettsioses from the coastal belt of Sri Lanka- a case report(BioMed Central, 2017) Luke, N.; Munasinghe, H.; Balasooriya, L.; Premaratna, R.BACKGROUND: Spotted fever group rickettsioses (SFGR) transmitted mostly by ticks are increasingly discovered around the World and some of them are either re-emerging or emerging in Sri Lanka. Accidental human infections caused by these vector borne zoonotic diseases generally give rise to nonspecific acute febrile illnesses which can be complicated by multi organ involvement carrying high morbidity and mortality. Nonspecific clinical features and non-availability of early diagnostic facilities are known to result in delay in the diagnosis of rickettsial infections. Therefore, awareness of their prevalence and more importantly their clinical features would be help in the early diagnosis and institution of appropriate therapy. CASE PRESENTATION: A 39-year-old otherwise healthy female presented with an acute febrile illness complicated by severe small joint and large joint arthritis, jaundice, acute kidney injury and disseminated intravascular coagulation (DIC) mimicking palindromic rheumatism or severe sepsis. She later developed a widespread fern-leaf pattern necrotic skin rash with evidence of vasculitis on the palms and soles, aiding the clinical diagnosis of SFGR. She had very high antibody titres against R. conorii antigen confirming the diagnosis and recovered completely with anti-rickettsial therapy. CONCLUSION: We feel that clinicians should be aware of the unusual clinical presentations such as purpura fulminans and 'fern-leaf' pattern necrotic skin rash of SFGR infection. Such knowledge would not only benefit those who practice in tropics with limited diagnostic facilities but also would improve the management of acute febrile illness in returning travelers who visit endemic areas.