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BACKGROUND: Acute respiratory tract infections (ARTIs) are a common reason for antibiotic overuse worldwide. We previously showed that over 80% of outpatients presenting to a tertiary care hospital in Sri Lanka with influenza-like illness received antibiotic prescriptions, although almost half were later confirmed to have influenza. The purpose of this qualitative study was to assess Sri Lankan patients' and physicians' attitudes towards ARTI diagnosis and treatment. METHODS: Semi-structured interviews were conducted with 50 outpatients with ARTIs and five physicians in the Outpatient Department (OPD) at a large, public tertiary care hospital in southern Sri Lanka. Interviews were audio-recorded, transcribed, and analyzed for themes related to ARTI diagnosis and treatment. RESULTS: Patients frequently sought ARTI care in the public sector due to the receipt of free care and the perception that government hospitals carried a sense of responsibility for patients' health. Patients reported multiple medical visits for their illnesses of short duration and many indicated that they were seeking care in the OPD while at the hospital for another reason. While patients generally expected to receive medication prescriptions at their visit, most patients were not specifically seeking an antibiotic prescription. However, more than 70% of patients received antibiotic prescriptions at their OPD visit. Physicians incorrectly perceived that patients desired antibiotics or "capsules," a common formulation of antibiotics dispensed in this outpatient setting, and cited patient demand as an important cause of antibiotic overuse. Physicians also indicated that high patient volume and fear of bacterial superinfection drove antibiotic overuse. CONCLUSIONS: Patients in this study were seeking medication prescriptions for their ARTIs, but physicians incorrectly perceived that antibiotic prescriptions were desired. High patient volume and fear of bacterial superinfection were also important factors in antibiotic overuse. Training of physicians regarding guideline-concordant management and dealing with diagnostic uncertainty, education of patients regarding ARTI etiology and management, and systematic changes in the public outpatient care structure may help decrease unnecessary antibiotic prescriptions for ARTIs in this setting.
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Antibacterianos/uso terapéutico , Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Prescripción Inadecuada , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Hospitales Públicos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Servicio Ambulatorio en Hospital , Pacientes Ambulatorios , Satisfacción del Paciente , Médicos , Investigación Cualitativa , Sri Lanka , Centros de Atención Terciaria , Adulto JovenRESUMEN
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.
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Antibacterianos , Infecciones del Sistema Respiratorio , Humanos , Masculino , Femenino , Sri Lanka/epidemiología , Antibacterianos/uso terapéutico , Niño , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Adulto , Adolescente , Preescolar , Persona de Mediana Edad , Estudios Prospectivos , Prevalencia , Lactante , Hospitalización , Adulto Joven , Polipéptido alfa Relacionado con Calcitonina/sangre , Anciano , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismoRESUMEN
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.
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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.
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Fibrilación Atrial , Leptospirosis , Fallo Hepático Agudo , Enfermedades Pulmonares , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aspartato Aminotransferasas , Fibrilación Atrial/complicaciones , Causas de Muerte , Hemoglobinas , Hemorragia/etiología , Leptospirosis/epidemiología , Fallo Hepático Agudo/complicaciones , Enfermedades Pulmonares/complicaciones , Sri Lanka/epidemiología , AdultoRESUMEN
Diagnostic limitations challenge management of clinically indistinguishable acute infectious illness globally. Gene expression classification models show great promise distinguishing causes of fever. We generated transcriptional data for a 294-participant (USA, Sri Lanka) discovery cohort with adjudicated viral or bacterial infections of diverse etiology or non-infectious disease mimics. We then derived and cross-validated gene expression classifiers including: 1) a single model to distinguish bacterial vs. viral (Global Fever-Bacterial/Viral [GF-B/V]) and 2) a two-model system to discriminate bacterial and viral in the context of noninfection (Global Fever-Bacterial/Viral/Non-infectious [GF-B/V/N]). We then translated to a multiplex RT-PCR assay and independent validation involved 101 participants (USA, Sri Lanka, Australia, Cambodia, Tanzania). The GF-B/V model discriminated bacterial from viral infection in the discovery cohort an area under the receiver operator curve (AUROC) of 0.93. Validation in an independent cohort demonstrated the GF-B/V model had an AUROC of 0.84 (95% CI 0.76-0.90) with overall accuracy of 81.6% (95% CI 72.7-88.5). Performance did not vary with age, demographics, or site. Host transcriptional response diagnostics distinguish bacterial and viral illness across global sites with diverse endemic pathogens.
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Infecciones Bacterianas , Virosis , Humanos , Virosis/diagnóstico , Virosis/genética , Biomarcadores , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/genética , Cambodia , AustraliaRESUMEN
Background: To develop effective antimicrobial stewardship programs (ASPs) for low- and middle-income countries (LMICs), it is important to identify key targets for improving antimicrobial use. We sought to systematically describe the prevalence and patterns of antimicrobial use in three LMIC hospitals. Methods: Consecutive patients admitted to the adult medical wards in three tertiary care hospitals in Tanzania, Kenya, and Sri Lanka were enrolled in 2018-2019. The medical record was reviewed for clinical information including type and duration of antimicrobials prescribed, indications for antimicrobial use, and microbiologic testing ordered. Results: A total of 3,149 patients were enrolled during the study period: 1,103 from Tanzania, 750 from Kenya, and 1,296 from Sri Lanka. The majority of patients were male (1,783, 56.6% overall) with a median age of 55 years (IQR 38-68). Of enrolled patients, 1,573 (50.0%) received antimicrobials during their hospital stay: 35.4% in Tanzania, 56.5% in Kenya, and 58.6% in Sri Lanka. At each site, the most common indication for antimicrobial use was lower respiratory tract infection (LRTI; 40.2%). However, 61.0% received antimicrobials for LRTI in the absence of LRTI signs on chest radiography. Among patients receiving antimicrobials, tools to guide antimicrobial use were under-utilized: microbiologic cultures in 12.0% and microbiology consultation in 6.5%. Conclusion: Antimicrobials were used in a substantial proportion of patients at tertiary care hospitals across three LMIC sites. Future ASP efforts should include improving LRTI diagnosis and treatment, developing antibiograms to direct empiric antimicrobial use, and increasing use of microbiologic tests.
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Antiinfecciosos , Programas de Optimización del Uso de los Antimicrobianos , Adulto , Anciano , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Países en Desarrollo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
[This corrects the article DOI: 10.1371/journal.pntd.0010091.].
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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.
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Dengue Grave/epidemiología , Dengue Grave/terapia , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Manejo de Caso , Niño , Estudios de Cohortes , Costo de Enfermedad , Virus del Dengue/genética , Virus del Dengue/inmunología , Virus del Dengue/aislamiento & purificación , Femenino , Hospitalización , Humanos , Masculino , Pacientes Ambulatorios/estadística & datos numéricos , Recuento de Plaquetas , Dengue Grave/sangre , Dengue Grave/virología , Sri Lanka/epidemiología , Atención Terciaria de Salud/estadística & datos numéricos , Resultado del Tratamiento , Adulto JovenRESUMEN
Viruses cause a wide spectrum of clinical disease, the majority being acute respiratory infections (ARI). In most cases, ARI symptoms are similar for different viruses although severity can be variable. The objective of this study was to understand the shared and unique elements of the host transcriptional response to different viral pathogens. We identified 162 subjects in the US and Sri Lanka with infections due to influenza, enterovirus/rhinovirus, human metapneumovirus, dengue virus, cytomegalovirus, Epstein Barr Virus, or adenovirus. Our dataset allowed us to identify common pathways at the molecular level as well as virus-specific differences in the host immune response. Conserved elements of the host response to these viral infections highlighted the importance of interferon pathway activation. However, the magnitude of the responses varied between pathogens. We also identified virus-specific responses to influenza, enterovirus/rhinovirus, and dengue infections. Influenza-specific differentially expressed genes (DEG) revealed up-regulation of pathways related to viral defense and down-regulation of pathways related to T cell and neutrophil responses. Functional analysis of entero/rhinovirus-specific DEGs revealed up-regulation of pathways for neutrophil activation, negative regulation of immune response, and p38MAPK cascade and down-regulation of virus defenses and complement activation. Functional analysis of dengue-specific up-regulated DEGs showed enrichment of pathways for DNA replication and cell division whereas down-regulated DEGs were mainly associated with erythrocyte and myeloid cell homeostasis, reactive oxygen and peroxide metabolic processes. In conclusion, our study will contribute to a better understanding of molecular mechanisms to viral infections in humans and the identification of biomarkers to distinguish different types of viral infections.
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Interferones/genética , Infecciones del Sistema Respiratorio/inmunología , Linfocitos T/fisiología , Virosis/genética , Virus/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Activación de Complemento , Femenino , Humanos , Inmunidad/genética , Interferones/metabolismo , Sistema de Señalización de MAP Quinasas , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Transcriptoma , Adulto JovenRESUMEN
BACKGROUND: Dengue is a major cause of acute febrile illness in Sri Lanka. Dengue has historically been considered an urban disease. In 2012-2013, we documented that acute dengue was surprisingly associated with self-reported rural residence in the Southern Province of Sri Lanka. METHODS: Patients admitted with an acute febrile illness were enrolled from June 2012-May 2013 in a cross-sectional surveillance study at the largest tertiary care hospital in the Southern Province. Acute dengue was diagnosed by serology and virology testing. Site visits were performed to collect residential geographical coordinates. Spatial variation in odds of acute dengue was modeled using a spatial generalized additive model predicted onto a grid of coordinate pairs covering the Southern Province. RESULTS: Of 800 patients, 333 (41.6%) had laboratory-confirmed acute dengue. Dengue was spatially heterogeneous (local probability of acute dengue 0.26 to 0.42). There were higher than average odds of acute dengue in the rural northeast of the Southern Province and lower than average odds in the urbanized southwest of the Southern Province, including the city Galle. CONCLUSIONS: Our study further affirms the emergence of dengue in rural southern Sri Lanka and highlights both the need for real-time geospatial analyses to optimize public health activities as well as the importance of strengthening dengue surveillance in non-urban areas.
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Dengue , Estudios Transversales , Dengue/epidemiología , Fiebre , Humanos , Salud Pública , Sri Lanka/epidemiologíaRESUMEN
BACKGROUND: Pathogen-based diagnostics for acute respiratory infection (ARI) have limited ability to detect etiology of illness. We previously showed that peripheral blood-based host gene expression classifiers accurately identify bacterial and viral ARI in cohorts of European and African descent. We determined classifier performance in a South Asian cohort. METHODS: Patients ≥15 years with fever and respiratory symptoms were enrolled in Sri Lanka. Comprehensive pathogen-based testing was performed. Peripheral blood ribonucleic acid was sequenced and previously developed signatures were applied: a pan-viral classifier (viral vs nonviral) and an ARI classifier (bacterial vs viral vs noninfectious). RESULTS: Ribonucleic acid sequencing was performed in 79 subjects: 58 viral infections (36 influenza, 22 dengue) and 21 bacterial infections (10 leptospirosis, 11 scrub typhus). The pan-viral classifier had an overall classification accuracy of 95%. The ARI classifier had an overall classification accuracy of 94%, with sensitivity and specificity of 91% and 95%, respectively, for bacterial infection. The sensitivity and specificity of C-reactive protein (>10 mg/L) and procalcitonin (>0.25 ng/mL) for bacterial infection were 100% and 34%, and 100% and 41%, respectively. CONCLUSIONS: Previously derived gene expression classifiers had high predictive accuracy at distinguishing viral and bacterial infection in South Asian patients with ARI caused by typical and atypical pathogens.
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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.
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Infecciones del Sistema Respiratorio , Adulto , Niño , Estudios Transversales , Brotes de Enfermedades , Humanos , Lactante , Estudios Prospectivos , Infecciones del Sistema Respiratorio/epidemiología , Sri Lanka/epidemiologíaRESUMEN
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.
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Antiinfecciosos/uso terapéutico , Unidades Hospitalarias/estadística & datos numéricos , Hospitales Públicos/estadística & datos numéricos , Prescripción Inadecuada/estadística & datos numéricos , Adulto , Programas de Optimización del Uso de los Antimicrobianos , Estudios Transversales , Farmacorresistencia Microbiana , Femenino , Adhesión a Directriz , Encuestas de Atención de la Salud , Unidades Hospitalarias/clasificación , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Sri Lanka , Adulto JovenRESUMEN
The contribution of respiratory viruses to acute febrile illness (AFI) burden is poorly characterized. We describe the prevalence, seasonality, and clinical features of respiratory viral infection among AFI admissions in Sri Lanka. We enrolled AFI patients ≥ 1 year of age admitted to a tertiary care hospital in southern Sri Lanka, June 2012-October 2014. We collected epidemiologic/clinical data and a nasal or nasopharyngeal sample that was tested using polymerase chain reaction (Luminex NxTAG, Austin, TX). We determined associations between weather data and respiratory viral activity using the Spearman correlation and assessed respiratory virus seasonality using a Program for Appropriate Technology definition. Bivariable and multivariable regression analyses were conducted to identify features associated with respiratory virus detection. Among 964 patients, median age was 26.2 years (interquartile range 14.6-39.9) and 646 (67.0%) were male. One-fifth (203, 21.1%) had respiratory virus detected: 13.9% influenza, 1.4% human enterovirus/rhinovirus, 1.4% parainfluenza virus, 1.1% respiratory syncytial virus, and 1.1% human metapneumovirus. Patients with respiratory virus identified were younger (median 9.8 versus 27.7 years, P < 0.001) and more likely to have respiratory signs and symptoms. Influenza A and respiratory viral activity peaked in February-June each year. Maximum daily temperature was associated with influenza and respiratory viral activity (P = 0.03 each). Patients with respiratory virus were as likely as others to be prescribed antibiotics (55.2% versus 52.6%, P = 0.51), and none reported prior influenza vaccination. Respiratory viral infection was a common cause of AFI. Improved access to vaccines and respiratory diagnostics may help reduce disease burden and inappropriate antibiotic use.
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Fiebre/epidemiología , Fiebre/etiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Virosis/diagnóstico , Virosis/epidemiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Estaciones del Año , Sri Lanka/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Dengue is a leading cause of fever and mimics other acute febrile illnesses (AFI). In 2009, the World Health Organization (WHO) revised criteria for clinical diagnosis of dengue. METHODOLOGY/PRINCIPAL FINDINGS: The new WHO 2009 classification of dengue divides suspected cases into three categories: dengue without warning signs, dengue with warning signs and severe dengue. We evaluated the WHO 2009 classification vs physicians' subjective clinical diagnosis (gestalt clinical impression) in a large cohort of patients presenting to a tertiary care center in southern Sri Lanka hospitalized with acute febrile illness. We confirmed acute dengue in 388 patients (305 adults ≥ 18 years and 83 children), including 103 primary and 245 secondary cases, of 976 patients prospectively enrolled with AFI. At presentation, both adults and children with acute dengue were more likely than those with other AFI to have leukopenia and thrombocytopenia. Additionally, adults were more likely than those with other AFI to have joint pain, higher temperatures, and absence of crackles on examination whereas children with dengue were more likely than others to have sore throat, fatigue, oliguria, and elevated hematocrit and transaminases. Similarly, presence of joint pain, thrombocytopenia, and absence of cough were independently associated with secondary vs primary dengue in adults whereas no variables were different in children. The 2009 WHO dengue classification was more sensitive than physicians' clinical diagnosis for identification of acute dengue (71.5% vs 67.1%), but was less specific. However, despite the absence of on-site diagnostic confirmation of dengue, clinical diagnosis was more sensitive on discharge (75.2%). The 2009 WHO criteria classified almost 75% as having warning signs, even though only 9 (2.3%) patients had evidence of plasma leakage and 16 (4.1%) had evidence of bleeding. CONCLUSIONS/SIGNIFICANCE: In a large cohort with AFI, we identified features predictive of dengue vs other AFI and secondary vs primary dengue in adults versus children. The 2009 WHO dengue classification criteria had high sensitivity but low specificity compared to physicians' gestaldt diagnosis. Large cohort studies will be needed to validate the diagnostic yield of clinical impression and specific features for dengue relative to the 2009 WHO classification criteria.
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Dengue/clasificación , Dengue/diagnóstico , Epidemias , Organización Mundial de la Salud , Enfermedad Aguda/epidemiología , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Dengue/complicaciones , Dengue/epidemiología , Virus del Dengue/genética , Virus del Dengue/aislamiento & purificación , Femenino , Fiebre/clasificación , Fiebre/diagnóstico , Fiebre/epidemiología , Hospitalización , Humanos , Leucopenia/epidemiología , Leucopenia/etiología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Dengue Grave/diagnóstico , Dengue Grave/epidemiología , Índice de Severidad de la Enfermedad , Sri Lanka/epidemiología , Centros de Atención Terciaria , Trombocitopenia/epidemiología , Trombocitopenia/etiología , Adulto JovenRESUMEN
In tropical and subtropical settings, the epidemiology of viral acute respiratory tract infections varies widely between countries. We determined the etiology, seasonality, and clinical presentation of viral acute respiratory tract infections among outpatients in southern Sri Lanka. From March 2013 to January 2015, we enrolled outpatients presenting with influenza-like illness (ILI). Nasal/nasopharyngeal samples were tested in duplicate using antigen-based rapid influenza testing and multiplex polymerase chain reaction (PCR) for respiratory viruses. Monthly proportion positive was calculated for each virus. Bivariable and multivariable logistic regression were used to identify associations between sociodemographic/clinical information and viral detection. Of 571 subjects, most (470, 82.3%) were ≥ 5 years of age and 53.1% were male. A respiratory virus was detected by PCR in 63.6% (N = 363). Common viral etiologies included influenza (223, 39%), human enterovirus/rhinovirus (HEV/HRV, 14.5%), respiratory syncytial virus (RSV, 4.2%), and human metapneumovirus (hMPV, 3.9%). Both ILI and influenza showed clear seasonal variation, with peaks from March to June each year. RSV and hMPV activity peaked from May to July, whereas HEV/HRV was seen year-round. Patients with respiratory viruses detected were more likely to report pain with breathing (odds ratio [OR] = 2.60, P = 0.003), anorexia (OR = 2.29, P < 0.001), and fatigue (OR = 2.00, P = 0.002) compared with patients with no respiratory viruses detected. ILI showed clear seasonal variation in southern Sri Lanka, with most activity during March to June; peak activity was largely due to influenza. Targeted infection prevention activities such as influenza vaccination in January-February may have a large public health impact in this region.
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Enfermedad Aguda/epidemiología , Pacientes Ambulatorios/estadística & datos numéricos , Infecciones del Sistema Respiratorio/epidemiología , Virosis/epidemiología , Virus/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Prevalencia , Infecciones del Sistema Respiratorio/virología , Estaciones del Año , Sri Lanka/epidemiología , Adulto JovenRESUMEN
The four serotypes of dengue virus (DENV-1, -2, -3, and -4) have had a rapidly expanding geographic range and are now endemic in over 100 tropical and subtropical countries. Sri Lanka has experienced periodic dengue outbreaks since the 1960s, but since 1989 epidemics have become progressively larger and associated with more severe disease. The dominant virus in the 2012 epidemic was DENV-1, but DENV-4 infections were also commonly observed. DENV-4 transmission was first documented in Sri Lanka when it was isolated from a traveler in 1978, but has been comparatively uncommon since dengue surveillance began in the early 1980s. To better understand the molecular epidemiology of DENV-4 infections in Sri Lanka, we conducted whole-genome sequencing on dengue patient samples from two different geographic locations. Phylogenetic analysis indicates that all sequenced DENV-4 strains belong to genotype 1 and are most closely related to DENV-4 viruses previously found in Sri Lanka and those recently found to be circulating in India and Pakistan.
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Virus del Dengue/genética , Dengue/epidemiología , Dengue/virología , Epidemias , Serogrupo , Virus del Dengue/clasificación , Humanos , Filogenia , Sri Lanka/epidemiologíaRESUMEN
BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) are increasingly reported as pathogens in urinary tract infections (UTIs). However, in Sri Lanka, the clinical and molecular epidemiology of ESBL-PE implicated in UTIs has not been well described. MATERIALS AND METHODS: We conducted prospective, laboratory-based surveillance from October to December 2013 at a tertiary care hospital in southern Sri Lanka and enrolled patients ≥1 year of age with clinically relevant UTIs due to ESBL-PE. Isolate identity, antimicrobial drug susceptibility, and ESBL production were determined. Presence of ß-lactamase genes, bla(SHV), bla(TEM), and bla(CTX-M), was identified by polymerase chain reaction. RESULTS: During the study period, Enterobacteriaceae were detected in 184 urine samples, with 74 (40.2%) being ESBL producers. Among 47 patients with ESBL-PE who had medical records available, 38 (80.9%) had clinically significant UTIs. Most UTIs (63.2%) were community acquired and 34.2% were in patients with diabetes. Among 36 cultured ESBL-PE isolates, significant susceptibility (>80%) was only retained to amikacin and the carbapenems. The group 1 bla(CTX-M) gene was present in 90.0% of Escherichia coli isolates and all Klebsiella pneumoniae and Enterobacter cloacae isolates. The bla(SHV) and bla(TEM) genes were more common in K. pneumoniae (75% and 50%) and E. cloacae (50% and 50%) isolates than in E. coli (10% and 20%) isolates, respectively. CONCLUSION: The majority of UTIs caused by ESBL-PE were acquired in the community and due to organisms carrying the group 1 CTX-M ß-lactamase. Further epidemiologic studies of infections due to ESBL-PE are urgently needed to better prevent and treat these infections in South Asia.
RESUMEN
BACKGROUND: Dengue is a frequent cause of acute febrile illness with an expanding global distribution. Since the 1960s, dengue in Sri Lanka has been documented primarily along the heavily urbanized western coast with periodic shifting of serotypes. Outbreaks from 2005-2008 were attributed to a new clade of DENV-3 and more recently to a newly introduced genotype of DENV-1. In 2007, we conducted etiologic surveillance of acute febrile illness in the Southern Province and confirmed dengue in only 6.3% of febrile patients, with no cases of DENV-1 identified. To re-evaluate the importance of dengue as an etiology of acute febrile illness in this region, we renewed fever surveillance in the Southern Province to newly identify and characterize dengue. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional surveillance study was conducted at the largest tertiary care hospital in the Southern Province from 2012-2013. A total of 976 patients hospitalized with acute undifferentiated fever were enrolled, with 64.3% male and 31.4% children. Convalescent blood samples were collected from 877 (89.6%). Dengue virus isolation, dengue RT-PCR, and paired IgG ELISA were performed. Acute dengue was confirmed as the etiology for 388 (39.8%) of 976 hospitalizations, with most cases (291, 75.0%) confirmed virologically and by multiple methods. Among 351 cases of virologically confirmed dengue, 320 (91.2%) were due to DENV-1. Acute dengue was associated with self-reported rural residence, travel, and months having greatest rainfall. Sequencing of selected dengue viruses revealed that sequences were most closely related to those described from China and Southeast Asia, not nearby India. CONCLUSIONS/SIGNIFICANCE: We describe the first epidemic of DENV-1 in the Southern Province of Sri Lanka in a population known to be susceptible to this serotype because of prior study. Dengue accounted for 40% of acute febrile illnesses in the current study. The emergence of DENV-1 as the foremost serotype in this densely populated but agrarian population highlights the changing epidemiology of dengue and the need for continued surveillance and prevention.
Asunto(s)
Virus del Dengue/aislamiento & purificación , Dengue/epidemiología , Dengue/virología , Epidemias/estadística & datos numéricos , Monitoreo Epidemiológico , Enfermedad Aguda , Adolescente , Adulto , Anticuerpos Antivirales/sangre , China/epidemiología , Estudios Transversales , Dengue/prevención & control , Virus del Dengue/genética , Virus del Dengue/inmunología , Brotes de Enfermedades , Femenino , Fiebre , Genotipo , Humanos , Inmunoglobulina G/sangre , India/epidemiología , Masculino , Lluvia , Reacción en Cadena en Tiempo Real de la Polimerasa , Población Rural , Análisis de Secuencia de ADN , Sri Lanka/epidemiología , Viaje , Adulto JovenRESUMEN
Influenza accounts for a large burden of acute respiratory tract infections in high-income countries; data from lower-income settings are limited due to lack of confirmatory testing. Consecutive outpatients presenting to the largest tertiary care hospital in southern Sri Lanka were surveyed for influenza-like illness (ILI), defined as acute onset of fever ≥ 38.0°C and cough. Patients were administered a questionnaire and nasal/nasopharyngeal sampling for rapid influenza A/B testing. We enrolled 311 patients with ILI from March to November 2013: 170 (54.7%) children and 172 (55.3%) males. Approximately half (147, 47.3%) tested positive for influenza, but 253 (81.4%) were prescribed antibiotics. On bivariable analysis, symptoms associated with influenza included pain with breathing (P < 0.001), headache (P = 0.005), fatigue (P = 0.003), arthralgias (P = 0.003), and myalgias (P = 0.006) in children and pain with breathing (P = 0.01), vomiting (P = 0.03), and arthralgias (P = 0.03) in adults. Our final clinical predictive models had low sensitivity and fair specificity-50.0% (95% CI: 38.6-61.4%) and 83.2% (95% CI: 73.4-90.0%), respectively, in children and 52.2% (95% CI: 39.9-64.2%) and 81.4% (95% CI: 70.0-89.4%), respectively, in adults. Our study confirms the ability of rapid influenza testing to identify an influenza epidemic in a setting in which testing is not routinely available.