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1.
Am J Trop Med Hyg ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39378867

RESUMO

Lower respiratory tract infection (LRTI) is a common reason for hospitalization and antibacterial use globally. There is considerable overlap in the clinical presentation of bacterial and viral LRTIs. Low- or middle-income countries (LMICs) face the dual challenge of appropriately targeting antibacterials for bacterial LRTI while reducing inappropriate antibacterials for viral LRTI. We propose a framework by which an electronic clinical decision support tool (eCDST) for diagnosing LRTI and reducing unnecessary antibacterial use may be developed, validated, and prospectively evaluated in an LMIC. The developed tool would be data driven, low-cost, feasible in the local setting, adaptable based on resource availability, and updated in real time, with prospective assessment to identify its clinical impact. We draw upon our team's recent experience developing an eCDST for LRTI management in Sri Lanka. Publicly sharing such processes and data is valuable, such that we can collectively improve clinical care in LMICs and other settings.

2.
PLoS One ; 19(6): e0304690, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38861513

RESUMO

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.


Assuntos
Antibacterianos , Infecções Respiratórias , Humanos , Masculino , Feminino , Sri Lanka/epidemiologia , Antibacterianos/uso terapêutico , Criança , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Adulto , Adolescente , Pré-Escolar , Pessoa de Meia-Idade , Estudos Prospectivos , Prevalência , Lactente , Hospitalização , Adulto Jovem , Pró-Calcitonina/sangue , Idoso , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo
3.
Sci Rep ; 13(1): 22554, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110534

RESUMO

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.


Assuntos
Infecções Bacterianas , Viroses , Humanos , Viroses/diagnóstico , Viroses/genética , Biomarcadores , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/genética , Camboja , Austrália
5.
Vaccines (Basel) ; 11(5)2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37243036

RESUMO

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.

6.
Front Public Health ; 10: 848802, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548085

RESUMO

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.


Assuntos
Anti-Infecciosos , Gestão de Antimicrobianos , Adulto , Idoso , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Países em Desenvolvimento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
8.
Pharmaceuticals (Basel) ; 15(4)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35455433

RESUMO

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.

9.
PLoS Negl Trop Dis ; 15(12): e0010091, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34962920

RESUMO

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.


Assuntos
Dengue Grave/epidemiologia , Dengue Grave/terapia , Adolescente , Adulto , Anticorpos Antivirais/sangue , Administração de Caso , Criança , Estudos de Coortes , Efeitos Psicossociais da Doença , Vírus da Dengue/genética , Vírus da Dengue/imunologia , Vírus da Dengue/isolamento & purificação , Feminino , Hospitalização , Humanos , Masculino , Pacientes Ambulatoriais/estatística & dados numéricos , Contagem de Plaquetas , Dengue Grave/sangue , Dengue Grave/virologia , Sri Lanka/epidemiologia , Atenção Terciária à Saúde/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem
10.
Front Immunol ; 12: 741837, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777354

RESUMO

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.


Assuntos
Interferons/genética , Infecções Respiratórias/imunologia , Linfócitos T/fisiologia , Viroses/genética , Vírus/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Ativação do Complemento , Feminino , Humanos , Imunidade/genética , Interferons/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Transcriptoma , Adulto Jovem
11.
Am J Trop Med Hyg ; 105(6): 1690-1695, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34583336

RESUMO

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.


Assuntos
Antibacterianos/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Infecções Respiratórias/tratamento farmacológico , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos/legislação & jurisprudência , Antibacterianos/efeitos adversos , Feminino , Humanos , Masculino , Infecções Respiratórias/epidemiologia , Sri Lanka/epidemiologia , Inquéritos e Questionários , Adulto Jovem
12.
Antimicrob Resist Infect Control ; 10(1): 72, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931120

RESUMO

BACKGROUND: The timing of and risk factors for intestinal colonization with multidrug-resistant Enterobacteriaceae (MDRE) are still poorly understood in areas with high MDRE carriage. We determined the prevalence, timing, and risk factors associated with MDRE intestinal colonization among infants in southern Sri Lanka. METHODS: Women and their newborn children were enrolled within 48 h after delivery in southern Sri Lanka. Rectal swabs were collected from women and infants at enrollment and 4-6 weeks later. Enterobacteriaceae were isolated and identified as MDRE (positive for extended-spectrum ß-lactamases or carbapenem resistant) using standard microbiologic procedures. We used exact methods (Fisher's exact and Kruskal-Wallis tests) and multivariable logistic regression to identify sociodemographic and clinical features associated with MDRE intestinal colonization. Whole-genome sequencing was performed on selected MDRE isolates to identify phylogroups and antibiotic resistance-encoding genes were identified with NCBI's AMRfinder tool. RESULTS: Overall, 199 post-partum women and 199 infants were enrolled; 148/199 (74.4%) women and 151/199 (75.9%) infants were reassessed later in the community. Twenty-four/199 (12.1%) women and 3/199 (1.5%) infants displayed intestinal colonization with MDRE at enrollment, while 26/148 (17.6%) women and 24/151 (15.9%) infants displayed intestinal colonization with MDRE at the reassessment. While there were no risk factors associated with infant colonization at enrollment, multivariable analysis indicated that risk factors for infant colonization at reassessment included mother colonized at enrollment (aOR = 3.62) or reassessment (aOR = 4.44), delivery by Cesarean section (aOR = 2.91), and low birth weight (aOR = 5.39). Of the 20 MDRE isolates from infants that were sequenced, multilocus sequence typing revealed that 6/20 (30%) were clustered on the same branch as MDRE isolates found in the respective mothers. All sequenced isolates for mothers (47) and infants (20) had at least one ESBL-producing gene. Genes encoding fosfomycin resistance were found in 33/47 (70%) of mothers' isolates and 16/20 (80%) of infants' isolates and genes encoding resistance to colistin were found in one (2%) mother's isolate. CONCLUSIONS: Our results suggest that a substantial proportion of infants undergo MDRE intestinal colonization within 6 weeks of birth, potentially due to postnatal rather than intranatal transmission.


Assuntos
Farmacorresistência Bacteriana Múltipla , Infecções por Enterobacteriaceae/epidemiologia , Adulto , Enterobacteriaceae/efeitos dos fármacos , Feminino , Hospitais de Ensino , Humanos , Recém-Nascido , Masculino , Gravidez , Reto/microbiologia , Sri Lanka/epidemiologia , Sequenciamento Completo do Genoma
13.
Antimicrob Resist Infect Control ; 10(1): 60, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33766135

RESUMO

BACKGROUND: Antimicrobial resistance has been named as one of the top ten threats to public health in the world. Hospital-based antimicrobial stewardship programs (ASPs) can help reduce antimicrobial resistance. The purpose of this study was to determine perceived barriers to the development and implementation of ASPs in tertiary care centers in three low- and middle-income countries (LMICs). METHODS: Interviews were conducted with 45 physicians at tertiary care hospitals in Sri Lanka (n = 22), Kenya (12), and Tanzania (11). Interviews assessed knowledge of antimicrobial resistance and ASPs, current antimicrobial prescribing practices, access to diagnostics that inform antimicrobial use, receptiveness to ASPs, and perceived barriers to implementing ASPs. Two independent reviewers coded the interviews using principles of applied thematic analysis, and comparisons of themes were made across the three sites. RESULTS: Barriers to improving antimicrobial prescribing included prohibitively expensive antimicrobials, limited antimicrobial availability, resistance to changing current practices regarding antimicrobial prescribing, and limited diagnostic capabilities. The most frequent of these barriers in all three locations was limited drug availability. Many physicians in all three sites had not heard of ASPs before the interviews. Improved education was a suggested component of ASPs at all three sites. The creation of guidelines was also recommended, without prompting, by interviewees at all three sites. Although most participants felt microbiological results were helpful in tailoring antibiotic courses, some expressed distrust of laboratory culture results. Biomarkers like erythrocyte sedimentation rate and c-reactive protein were not felt to be specific enough to guide antimicrobial therapy. Despite limited or no prior knowledge of ASPs, most interviewees were receptive to implementing protocols that would include documentation and consultation with ASPs regarding antimicrobial prescribing. CONCLUSIONS: Our study highlighted several important barriers to implementing ASPs that were shared between three tertiary care centers in LMICs. Improving drug availability, enhancing availability of and trust in microbiologic data, creating local guidelines, and providing education to physicians regarding antimicrobial prescribing are important steps that could be taken by ASPs in these facilities.


Assuntos
Gestão de Antimicrobianos , Países em Desenvolvimento , Implementação de Plano de Saúde , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/economia , Antibacterianos/provisão & distribuição , Farmacorresistência Bacteriana , Humanos , Quênia , Médicos , Pesquisa Qualitativa , Sri Lanka , Tanzânia , Centros de Atenção Terciária
14.
BMC Infect Dis ; 21(1): 97, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478430

RESUMO

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.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Antibacterianos/uso terapêutico , Prescrições/estatística & dados numéricos , Doenças Respiratórias/tratamento farmacológico , Adolescente , Adulto , Gestão de Antimicrobianos , Criança , Estudos Transversais , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Padrões de Prática Médica , Prevalência , Doenças Respiratórias/diagnóstico , Doenças Respiratórias/epidemiologia , Sri Lanka/epidemiologia , Centros de Atenção Terciária , Adulto Jovem
15.
BMJ Open ; 10(11): e040612, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-33158834

RESUMO

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.


Assuntos
Infecções Respiratórias , Adulto , Criança , Estudos Transversais , Surtos de Doenças , Humanos , Lactente , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Sri Lanka/epidemiologia
16.
Open Forum Infect Dis ; 7(6): ofaa194, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32617371

RESUMO

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.

17.
Molecules ; 25(8)2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32326068

RESUMO

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.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Humanos , Concentração Inibidora 50 , Medicina Tradicional , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Prostaglandina-E Sintases/metabolismo , Sri Lanka
18.
Trans R Soc Trop Med Hyg ; 114(6): 408-414, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31885050

RESUMO

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.


Assuntos
Dengue , Estudos Transversais , Dengue/epidemiologia , Febre , Humanos , Saúde Pública , Sri Lanka/epidemiologia
19.
BMJ Glob Health ; 4(2): e001291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30997171

RESUMO

BACKGROUND: Acute respiratory infections are a common reason for antibiotic overuse. We previously showed that providing Sri Lankan clinicians with positive rapid influenza test results was associated with a reduction in antibiotic prescriptions. The economic impact of influenza diagnostic strategies is unknown. METHODS: We estimated the incremental cost per antibiotic prescription avoided with three diagnostic strategies versus standard care when managing Sri Lankan outpatients with influenza-like illness (ILI): (1) influenza clinical prediction tool, (2) targeted rapid influenza testing and (3) universal rapid influenza testing. We compared findings with literature-based estimates of the cost of antimicrobial resistance attributable to each antibiotic prescription. RESULTS: Standard care was less expensive than other strategies across all parameter values in one-way sensitivity analyses. The incremental cost per antibiotic prescription avoided with clinical prediction versus standard care was US$3.0, which was lower than the base-case estimate of the cost of antimicrobial resistance per ILI antibiotic prescription (US$12.5). The incremental cost per antibiotic prescription avoided with targeted testing and universal testing versus standard care were both higher than the base-case cost of antimicrobial resistance per ILI antibiotic prescription: US$49.1 and US$138.3, respectively. To obtain a cost-effectiveness ratio lower than US$12.5 with targeted testing versus standard care, the test price must be

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