Prevalence and predictors of antibiotic prescription among patients hospitalized with viral lower respiratory tract infections in Southern Province, Sri Lanka.

BACKGROUND: Antimicrobial overprescription is common for lower respiratory tract infections (LRTI), as viral and bacterial infections generally present with similar clinical features. Overprescription is associated with downstream antimicrobial resistance. This study aims to identify the prevalence and predictors of antibiotic prescription among patients hospitalized with viral LRTI. METHODS: A prospective cohort study was conducted among patients aged ≥1 year hospitalized with viral LRTI in a tertiary care hospital in Southern Province, Sri Lanka from 2018-2021. Demographic, clinical, and laboratory data were recorded. Nasopharyngeal and blood samples were collected for multiplex polymerase chain reaction testing for 21 respiratory pathogens and procalcitonin (PCT) detection, respectively. Demographic and clinical features associated with antibiotic prescription were identified using Chi Square and t-tests; significant variables (p<0.05) were further included in multivariable logistic regression models. The potential impact of biomarker testing on antibiotic prescription was simulated using standard c-reactive protein (CRP) and PCT cut-offs. RESULTS: Of 1217 patients enrolled, 438 (36.0%) had ≥1 respiratory virus detected, with 48.4% of these patients being male and 30.8% children. Influenza A (39.3%) and human rhinovirus/ enterovirus (28.3%) were most commonly detected. A total of 114 (84.4%) children and 266 (87.8%) adults with respiratory viruses were treated with antibiotics. Among children, neutrophil percentage (median 63.6% vs 47.6%, p = 0.04) was positively associated with antibiotic prescription. Among adults, headache (60.6% vs 35.1%, p = 0.003), crepitations/crackles (55.3% vs 21.6%, p<0.001), rhonchi/wheezing (42.9% vs 18.9%, p = 0.005), and chest x-ray opacities (27.4% vs 8.1%, p = 0.01) were associated with antibiotic prescription. Access to CRP and procalcitonin test results could have potentially decreased inappropriate antibiotic prescription in this study by 89.5% and 83.3%, respectively. CONCLUSIONS: High proportions of viral detection and antibiotic prescription were observed among a large inpatient cohort with LRTI. Increased access to point-of-care biomarker testing may improve antimicrobial prescription.

Pulmonary haemorrhage as a frequent cause of death among patients with severe complicated Leptospirosis in Southern Sri Lanka.

BACKGROUND: Leptospirosis is a tropical disease associated with life threatening complications. Identifying clinical and investigation-based parameters that predict mortality and morbidity is vital to provide optimal supportive care. METHODS: We conducted an observational study in an endemic setting, in the southern Sri Lanka. Consecutive patients having complicated leptospirosis were recruited over 18 months. Clinical, investigational and treatment data were collected and the predictors of mortality were analysed. RESULTS: Out of 88 patients having complicated leptospirosis, 89% were male. Mean age was 47yrs (±16.0). Among the total major complications 94.3% had acute kidney injury, 38.6% pulmonary haemorrhages, 12.5% fulminant hepatic failure, 60.2% hemodynamic instability and 33% myocarditis. An acute significant reduction of haemoglobin (Hb) was observed in 79.4% of patients with pulmonary haemorrhage. The mean of the highest haemoglobin reduction in patients with pulmonary haemorrhage was 3.1g/dL. The presence of pulmonary haemorrhage (PH) and hemodynamic instability within first 48 hours of admission significantly predicted mortality (p<0.05) in severe leptospirosis. Additionally, within first 48 hours of admission, elevated SGOT (AST), presence of atrial fibrillation, presence of significant haemoglobin reduction, higher number of inotropes used, prolonged shock, invasive ventilation and admission to ICU significantly predicted mortality. Out of major complications during the first week after admission, pulmonary haemorrhage and fulminant hepatic failure (FHF) combination had significant adjusted odds of mortality (OR = 6.5 and 4.8, p<0.05). Six patients with severe respiratory failure due to PH underwent ECMO and four survived. The overall mortality in complicated leptospirosis was 17%. In PH and FHF, the mortality rate was higher reaching 35.4% and 54.5%, respectively. CONCLUSIONS: Within first 48 hours of admission, major complications such as pulmonary haemorrhage and haemodynamic instability and other parameters such as atrial fibrillation, acute haemoglobin reduction, elevated SGOT level could be used as early parameters predictive of mortality in severe leptospirosis. PH and FHF during the first week of admission in leptospirosis are associated with high morbidity and mortality requiring prolonged ICU care and hospitalisation. Above parameters could be used as parameters indicating severity for triaging and intensifying treatment. Using ECMO is a plausible treatment option in patients with severe pulmonary haemorrhage.

Influenza Vaccination Implementation in Sri Lanka: A Cost-Effectiveness Analysis.

Influenza causes an estimated 3 to 5 million cases of severe illness annually, along with substantial morbidity and mortality, particularly in low- and middle-income countries (LMICs). Currently, Sri Lanka has no influenza vaccination policies and does not offer vaccination within the public healthcare sector. Therefore, we performed a cost-effectiveness analysis of influenza vaccine implementation for the Sri Lankan population. We designed a static Markov model that followed a population cohort of Sri Lankans in three age groups, 0-4, 5-64, and 65+ years, through two potential scenarios: trivalent inactivated vaccination (TIV) and no TIV across twelve-monthly cycles using a governmental perspective at the national level. We also performed probabilistic and one-way sensitivity analyses to identify influential variables and account for uncertainty. The vaccination model arm reduced influenza outcomes by 20,710 cases, 438 hospitalizations, and 20 deaths compared to no vaccination in one year. Universal vaccination became cost-effective at approximately 98.01% of Sri Lanka's 2022 GDP per capita (incremental cost-effectiveness ratio = 874,890.55 Rs/DALY averted; 3624.84 USD/DALY averted). Results were most sensitive to the vaccine coverage in the 5-64-year-old age group, the cost of the influenza vaccine dose in the 5-64-years-old age group, vaccine effectiveness in the under-5-years-old age group, and the vaccine coverage in the under-5-years-old age group. No value for a variable within our estimated ranges resulted in ICERs above Rs. 1,300,000 (USD 5386.15) per DALY adverted. Providing influenza vaccines was considered highly cost-effective compared to no vaccines. However, large-scale national studies with improved data are needed to better inform estimates and determine the impact of vaccination implementation.

Correction: Outcomes among children and adults at risk of severe dengue in Sri Lanka: Opportunity for outpatient case management in countries with high disease burden.

[This corrects the article DOI: 10.1371/journal.pntd.0010091.].

Plectranthus zeylanicus: A Rich Source of Secondary Metabolites with Antimicrobial, Disinfectant and Anti-Inflammatory Activities.

Plectranthus zeylanicus Benth is used in Sri Lankan folk medicine as a remedy for inflammatory conditions and microbial infections. Our previous investigations revealed potent 5-lipoxygenase (5-LO) inhibitory activity in lipophilic extracts of this plant, supporting its anti-inflammatory potential. In-depth studies on the antimicrobial activity have not been conducted and the bioactive ingredients remained elusive. As a continuation of our previous work, the present investigation was undertaken to evaluate the antimicrobial activity of different extracts of P. zeylanicus and to isolate and characterize bioactive secondary metabolites. Different organic extracts of this plant were analyzed for their antibacterial activity, and the most active extract, i.e., dichloromethane extract, was subjected to bioactivity-guided fractionation, which led to the isolation of 7α-acetoxy-6ß-hydroxyroyleanone. This compound displayed strong antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimum inhibitory concentration of 62.5 µg/mL, and its disinfectant capacity was comparable to the potency of a commercial disinfectant. Moreover, 7α-acetoxy-6ß-hydroxyroyleanone inhibits 5-LO with IC50 values of 1.3 and 5.1 µg/mL in cell-free and cell-based assays, respectively. These findings rationalize the ethnopharmacological use of P. zeylanicus as antimicrobial and anti-inflammatory remedy.

Outcomes among children and adults at risk of severe dengue in Sri Lanka: Opportunity for outpatient case management in countries with high disease burden.

BACKGROUND: Healthcare systems in dengue-endemic countries are often overburdened due to the high number of patients hospitalized according to dengue management guidelines. We systematically evaluated clinical outcomes in a large cohort of patients hospitalized with acute dengue to support triaging of patients to ambulatory versus inpatient management in the future. METHODS/PRINCIPAL FINDINGS: From June 2017- December 2018, we conducted surveillance among children and adults with fever within the prior 7 days who were hospitalized at the largest tertiary-care (1,800 bed) hospital in the Southern Province, Sri Lanka. Patients who developed platelet count ≤100,000/µL (threshold for hospital admission in Sri Lanka) and who met at least two clinical criteria consistent with dengue were eligible for enrollment. We confirmed acute dengue by testing sera collected at enrollment for dengue NS1 antigen or IgM antibodies. We defined primary outcomes as per the 1997 and 2009 World Health Organization (WHO) classification criteria: dengue hemorrhagic fever (DHF; WHO 1997), dengue shock syndrome (DSS; WHO 1997), and severe dengue (WHO 2009). Overall, 1064 patients were confirmed as having acute dengue: 318 (17.4%) by NS1 rapid antigen testing and 746 (40.7%) by IgM antibody testing. Of these 1064 patients, 994 (93.4%) were adults ≥18 years and 704 (66.2%) were male. The majority (56, 80%) of children and more than half of adults (544, 54.7%) developed DHF during hospitalization, while 6 (8.6%) children and 22 (2.2%) adults developed DSS. Overall, 10 (14.3%) children and 113 (11.4%) adults developed severe dengue. A total of 2 (0.2%) patients died during hospitalization. CONCLUSIONS: One-half of patients hospitalized with acute dengue progressed to develop DHF and a very small number developed DSS or severe dengue. Developing an algorithm for triaging patients to ambulatory versus inpatient management should be the future goal to optimize utilization of healthcare resources in dengue-endemic countries.

Knowledge, Perceptions, and Attitudes Regarding Antibiotic Use for Lower Respiratory Tract Infections: Insights from Patients in Sri Lanka.

Antibiotic resistance is an emerging global public health threat. One of the main drivers of this threat is the inappropriate use of antibiotics. In Sri Lanka, antibiotic consumption is increasing, but little is known locally about how patients perceive antibiotics. We conducted a qualitative study to gain a better understanding of the knowledge, perceptions, and attitudes of patients regarding antibiotics and antibiotic resistance. Semi-structured interviews involving 18 patients with lower respiratory tract infection (LRTI) admitted to a large, public tertiary care hospital in southern Sri Lanka were conducted. Interviews were analyzed to identify themes regarding the patients' knowledge of LRTI etiology and treatment, perceptions and attitudes toward LRTI treatment, including antibiotics, and patient-physician communication. Most patients mentioned multiple care visits and the use of multiple pharmaceuticals prior to admission. Patients sought a quick resolution to their ailments and frequently visited several private physicians to obtain a satisfying answer. Self-medication was also common. Patients reused prescriptions for antibiotics, kept antibiotics for later use after prematurely stopping their course of treatment, and bought over-the-counter antibiotics. Patients' knowledge of disease etiology and antibiotics was poor. Only a few patients were aware of antibiotic resistance. Despite the desire to receive more information regarding disease and treatment, patient-provider communication was limited and mainly confined to prescription instructions. This qualitative study performed in Sri Lanka suggests that inappropriate use of antibiotics is a multifactorial problem. To improve antibiotic use, a multifactorial approach that includes educating the public, increasing awareness among physicians, and implementing systems-level changes to restrict access to antibiotics is urgently needed.

Point-prevalence survey of outpatient antibiotic prescription at a tertiary medical center in Sri Lanka: opportunities to improve prescribing practices for respiratory illnesses.

BACKGROUND: Inappropriate antibiotic use is linked to the spread of antimicrobial resistance worldwide, but there are limited systemic data on antibiotic utilization in low- and middle-income countries. The purpose of this study was to evaluate the prevalence and patterns of antibiotic prescription in an ambulatory care setting in Sri Lanka. METHODS: This cross-sectional survey was conducted at the Outpatient Department of a public tertiary medical center in Southern Province, Sri Lanka from February to April 2019. Among consecutive outpatients presenting for care, questionnaires were verbally administered to a systematic random sample to capture information about patient demographics, illness characteristics, and visit outcomes. Prescription data were obtained from the outpatient pharmacy's electronic prescribing system. RESULTS: Of 409 surveyed patients, 146 (35.7%) were prescribed an antibiotic. The most frequently prescribed agents were amoxicillin (41 patients, 28.1% of antibiotic recipients) and first-generation cephalosporins (38, 26.0%). Respiratory indications were the most common reason for antibiotic use, comprising 69 (47.3%) of all antibiotic prescriptions. Antibiotics were prescribed for 66.1% of patients presenting with cough and 78.8% of those presenting with rhinorrhea or nasal congestion. Among all antibiotic recipients, 6 (4.1%) underwent diagnostic studies. CONCLUSIONS: A high prevalence of antibiotic prescription was observed, in particular for treatment of respiratory conditions. These data support the need for improved antimicrobial stewardship in the Sri Lankan outpatient setting.

Outbreak of severe acute respiratory infection in Southern Province, Sri Lanka in 2018: a cross-sectional study.

OBJECTIVES: To determine aetiology of illness among children and adults presenting during outbreak of severe respiratory illness in Southern Province, Sri Lanka, in 2018. DESIGN: Prospective, cross-sectional study. SETTING: 1600-bed, public, tertiary care hospital in Southern Province, Sri Lanka. PARTICIPANTS: 410 consecutive patients, including 371 children and 39 adults, who were admitted with suspected viral pneumonia (passive surveillance) or who met case definition for acute respiratory illness (active surveillance) in May to June 2018. RESULTS: We found that cocirculation of influenza A (22.6% of cases), respiratory syncytial virus (27.8%) and adenovirus (AdV) (30.7%; type B3) was responsible for the outbreak. Mortality was noted in 4.5% of paediatric cases identified during active surveillance. Virus type and viral coinfection were not significantly associated with mortality. CONCLUSIONS: This is the first report of intense cocirculation of multiple respiratory viruses as a cause of an outbreak of severe acute respiratory illness in Sri Lanka, and the first time that AdV has been documented as a cause of a respiratory outbreak in the country. Our results emphasise the need for continued vigilance in surveying for known and emerging respiratory viruses in the tropics.

The Anti-Inflammatory and Antimicrobial Potential of Selected Ethnomedicinal Plants from Sri Lanka.

Traditional folk medicine in Sri Lanka is mostly based on plants and plant-derived products, however, many of these medicinal plant species are scientifically unexplored. Here, we evaluated the anti-inflammatory and antimicrobial potency of 28 different extracts prepared from seven popular medicinal plant species employed in Sri Lanka. The extracts were subjected to cell-based and cell-free assays of 5-lipoxygenase (5-LO), microsomal prostaglandin E2 synthase (mPGES)-1, and nitric oxide (NO) scavenging activity. Moreover, antibacterial and disinfectant activities were assessed. Characterization of secondary metabolites was achieved by gas chromatography coupled to mass spectrometric (GC-MS) analysis. n-Hexane- and dichloromethane-based extracts of Garcinia cambogia efficiently suppressed 5-LO activity in human neutrophils (IC50 = 0.92 and 1.39 µg/mL), and potently inhibited isolated human 5-LO (IC50 = 0.15 and 0.16 µg/mL) and mPGES-1 (IC50 = 0.29 and 0.49 µg/mL). Lipophilic extracts of Pothos scandens displayed potent inhibition of mPGES-1 only. A methanolic extract of Ophiorrhiza mungos caused significant NO scavenging activity. The lipophilic extracts of G. cambogia exhibited prominent antibacterial and disinfectant activities, and GC-MS analysis revealed the presence of fatty acids, sesquiterpenes and other types of secondary metabolites. Together, our results suggest the prospective utilization of G. cambogia as disinfective agent with potent anti-inflammatory properties.

Point-prevalence study of antimicrobial use in public hospitals in southern Sri Lanka identifies opportunities for improving prescribing practices.

A point-prevalence study of antimicrobial use among inpatients at 5 public hospitals in Sri Lanka revealed that 54.6% were receiving antimicrobials: 43.1% in medical wards, 68.0% in surgical wards, and 97.6% in intensive care wards. Amoxicillin-clavulanate was most commonly used for major indications. Among patients receiving antimicrobials, 31.0% received potentially inappropriate therapy.

Elevated pre-surgical CA15-3: does it predict the short-term disease-free survival of breast cancer patients without distant metastasis?

BACKGROUND: CA15-3 is the most commonly used tumor marker in breast cancer. Its prognostic role has been described in the metastatic setting, but the role of pre-surgical CA15-3 in the assessment of patients with breast cancer without metastasis has not been substantiated yet. METHODOLOGY: From February 2014 for a 2-year period, this prospective study included all patients who were diagnosed with primary breast cancer and underwent surgery at a tertiary care hospital. The serum level of CA15-3 was assessed on a pre-surgical blood sample and later at the 3-, 6-, 9-, and 12-month follow-up by enzyme-linked immunosorbent assay. Disease-free survival (DFS) was analyzed with a Kaplan-Meier model and log-rank test. RESULTS: We enrolled 195 patients (mean age ± SD 57.84 years ±13.819, range, 28-95) with breast cancer. The prevalence of elevated (≥30 U/mL) pre-surgical CA15-3 was 35.9%, and it reduced to 14.3% at 3 months after mastectomy. Pre-surgical CA15-3 had a significant association only with the size of the tumor (p=0.047). Patients who did not have elevated pre-surgical CA15-3 (≥30 U/mL) had the best short-term DFS, and it was worst when the pre-surgical CA15-3 was >100 U/mL (p=0.041). CONCLUSION: Elevated pre-surgical CA15-3 is a predictor of poor short-term DFS of patients with breast cancer without distant metastasis.

Lipophilic extracts of Leucas zeylanica, a multi-purpose medicinal plant in the tropics, inhibit key enzymes involved in inflammation and gout.

ETHNOPHARMACOLOGICAL RELEVANCE: Leucas zeylanica (L.) W.T. Aiton is a popular, multi-purpose medicinal plant in Sri Lanka but the pharmacological potential and the chemical profile have not been systematically investigated to understand and rationalize the reported ethnobotanical significance. AIM OF THE STUDY: The present study was undertaken to scientifically validate the traditional usage of this plant for the treatment of inflammatory conditions, gout and microbial infections. Inhibition of 5-lipoxygenase (5-LO), microsomal prostaglandin E2 synthase (mPGES)-1 and xanthine oxidase (XO) by different extracts of L. zeylanica was investigated to determine the anti-inflammatory and anti-gout activity, respectively. The antibacterial and antifungal activities were also studied and the relevant constituents in the bioactive extracts were tentatively identified. MATERIALS AND METHODS: Cell-free and/or cell-based assays were employed in order to investigate the effects of the extracts against the activity of human 5-LO, mPGES-1 and XO as well as to assess antioxidant properties. The antibacterial activity of the extracts was determined by the broth micro-dilution method against Gram positive and Gram negative bacteria including methicillin-resistant Staphylococcus aureus while the agar dilution method was employed to determine the anti-Candida activity. Gas chromatography coupled to mass spectrometric (GC-MS) analysis enabled the characterization of secondary metabolites in the extracts. RESULTS: The dichloromethane extract of L. zeylanica efficiently inhibited 5-LO activity in stimulated human neutrophils (IC50 = 5.5 µg/mL) and isolated human 5-LO and mPGES-1 (IC50 = 2.2 and 0.4 µg/mL). Potent inhibition of XO was observed by the same extract (IC50 = 47.5 µg/mL), which is the first report of XO-inhibitory activity of a Sri Lankan medicinal plant. Interestingly, significant radical scavenging activity was not observed by this extract. Only the n-hexane extract exhibited antibacterial activity against Staphylococcus aureus and Staphylococcus saprophyticus with a MIC of 250 µg/mL while the anti-Candida activity was moderate. GC-MS analysis revealed the presence of phytosterols, fatty acids, sesquiterpenes, diterpenes and several other types of secondary metabolites. CONCLUSIONS: Potent inhibition of 5-LO, mPGES-1 and XO rationalizes the ethnopharmacological use of L. zeylanica as anti-inflammatory and anti-gout remedy. Interestingly, the antimicrobial activities were not prominent, despite its wide utility as an antimicrobial medication.