Browsing by Author "Tillekeratne, L Gayani"
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Item Open Access Access to COVID-19 testing by individuals with housing insecurity during the early days of the COVID-19 pandemic in the United States: a scoping review.(Frontiers in public health, 2023-01) Johannesson, Jon M; Glover, William A; Petti, Cathy A; Veldman, Timothy H; Tsalik, Ephraim L; Taylor, Donald H; Hendren, Stephanie; Neighbors, Coralei E; Tillekeratne, L Gayani; Kennedy, Scott W; Harper, Barrie; Kibbe, Warren A; Corbie, Giselle; Cohen-Wolkowiez, Michael; Woods, Christopher W; Lee, Mark JIntroduction
The COVID-19 pandemic focused attention on healthcare disparities and inequities faced by individuals within marginalized and structurally disadvantaged groups in the United States. These individuals bore the heaviest burden across this pandemic as they faced increased risk of infection and difficulty in accessing testing and medical care. Individuals experiencing housing insecurity are a particularly vulnerable population given the additional barriers they face. In this scoping review, we identify some of the barriers this high-risk group experienced during the early days of the pandemic and assess novel solutions to overcome these barriers.Methods
A scoping review was performed following PRISMA-Sc guidelines looking for studies focusing on COVID-19 testing among individuals experiencing housing insecurity. Barriers as well as solutions to barriers were identified as applicable and summarized using qualitative methods, highlighting particular ways that proved effective in facilitating access to testing access and delivery.Results
Ultimately, 42 studies were included in the scoping review, with 143 barriers grouped into four categories: lack of cultural understanding, systemic racism, and stigma; medical care cost, insurance, and logistics; immigration policies, language, and fear of deportation; and other. Out of these 42 studies, 30 of these studies also suggested solutions to address them.Conclusion
A paucity of studies have analyzed COVID-19 testing barriers among those experiencing housing insecurity, and this is even more pronounced in terms of solutions to address those barriers. Expanding resources and supporting investigators within this space is necessary to ensure equitable healthcare delivery.Item Open Access Antibacterial Utilization for Febrile Illnesses and Laboratory-Confirmed Bloodstream Infections in Northern Tanzania.(Open forum infectious diseases, 2023-08) Moorthy, Ganga S; Madut, Deng B; Kilonzo, Kajiru G; Lwezaula, Bingileki F; Mbwasi, Ronald; Mmbaga, Blandina T; Ngocho, James S; Saganda, Wilbrod; Bonnewell, John P; Carugati, Manuela; Egger, Joseph R; Hertz, Julian T; Tillekeratne, L Gayani; Maze, Michael J; Maro, Venance P; Crump, John A; Rubach, Matthew PBackground
We describe antibacterial use in light of microbiology data and treatment guidelines for common febrile syndromes in Moshi, Tanzania.Methods
We compared data from 2 hospital-based prospective cohort studies, cohort 1 (2011-2014) and cohort 2 (2016-2019), that enrolled febrile children and adults. A study team member administered a standardized questionnaire, performed a physical examination, and collected blood cultures. Participants with bloodstream infection (BSI) were categorized as receiving effective or ineffective therapy based upon antimicrobial susceptibility interpretations. Antibacterials prescribed for treatment of pneumonia, urinary tract infection (UTI), or presumed sepsis were compared with World Health Organization and Tanzania Standard Treatment Guidelines. We used descriptive statistics and logistic regression to describe antibacterial use.Results
Among participants, 430 of 1043 (41.2%) and 501 of 1132 (44.3%) reported antibacterial use prior to admission in cohorts 1 and 2, respectively. During admission, 930 of 1043 (89.2%) received antibacterials in cohort 1 and 1060 of 1132 (93.6%) in cohort 2. Inpatient use of ceftriaxone, metronidazole, and ampicillin increased between cohorts (P ≤ .002 for each). BSI was detected in 38 (3.6%) participants in cohort 1 and 47 (4.2%) in cohort 2. Of 85 participants with BSI, 81 (95.3%) had complete data and 52 (64.2%) were prescribed effective antibacterials. Guideline-consistent therapy in cohort 1 and cohort 2 was as follows: pneumonia, 87.4% and 56.8%; UTI, 87.6% and 69.0%; sepsis, 84.4% and 61.2% (P ≤ .001 for each).Conclusions
Receipt of antibacterials for febrile illness was common. While guideline-consistent prescribing increased over time, more than one-third of participants with BSI received ineffective antibacterials.Item Open Access Antibiotic overuse for acute respiratory tract infections in Sri Lanka: a qualitative study of outpatients and their physicians.(BMC Fam Pract, 2018-03-01) Tillekeratne, L Gayani; Bodinayake, Champica K; Dabrera, Thushani; Nagahawatte, Ajith; Arachchi, Wasantha Kodikara; Sooriyaarachchi, Anoji; Stewart, Kearsley; Watt, Melissa; Østbye, Truls; Woods, Christopher WBACKGROUND: 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.Item Embargo Assessment of guideline-concordant antimicrobial prescription for inpatients with lower respiratory tract infection in southern Sri Lanka(2024) Wang, ShuruiBackground: Lower respiratory tract infection (LRTI) is one of the most common reasons for hospitalization globally. Inappropriate antimicrobial prescriptions are common for LRTI, which might lead to antimicrobial resistance (AMR) and poor patient outcomes. In this study, we identified the proportion of receiving appropriate antimicrobial prescriptions and features associated with inappropriate prescriptions among inpatients with LRTI in Sri Lanka. Methods: We conducted a point-prevalence study of antimicrobial prescription among inpatients at 5 public hospitals in southern Sri Lanka in June-August 2017. Sociodemographic and clinical data were extracted from the medical chart and descriptive analyses were performed. The appropriateness of prescriptions for LRTI was evaluated according to the 2016 National Guidelines by the Sri Lanka College of Microbiologists. Multivariable logistic regression was used to identify features associated with inappropriate antimicrobial prescriptions. Results: Of 935 surveyed patients who were receiving antimicrobials, 187 were receiving antimicrobials for the treatment of LRTI. Of these 187 patients, 121 (64.7%) were adults ≥18 years old, and 101 (54.0%) were male. The average number of antimicrobials per LRTI patient was 1.7±0.0. Adults and children received similar numbers (1.8±0.1 vs 1.5±0.1, respectively; P = 0.167), and penicillins, third-generation cephalosporins, and macrolides were the most commonly prescribed antimicrobials in both age groups. Only 65 (34.8%) patients received guideline-concordant therapies for LRTI. There was no difference in receiving guideline-concordant therapy among different age groups (≤5, 5-17, 18-64, ≥65 years old; P = 0.580) or ward types (medical, pediatric, mixed medical/ surgical ward, intensive care; P = 0.299). Among patients receiving inappropriate antimicrobial prescriptions, undertreatment accounted for the largest proportion (55.7%), followed by partially-concordant prescriptions (30.3%). The potential risk factors for non guideline-concordant antimicrobial prescription was the numbers of antimicrobials (OR, 0.10; 95% CI, 0.05-0.21), diabetes mellitus (OR, 5.22; 95% CI, 1.22-22.27), and methicillin-resistant Staphylococcus aureus (MRSA) treatment (OR, 4.96; 95% CI, 1.74-14.13). Conclusions: This study showed a high proportion of inappropriate prescriptions of antimicrobials for LRTI in southern Sri Lanka. Further studies are needed to identify reasons for inappropriate prescriptions and targets for antimicrobial stewardship interventions.
Item Open Access Barriers to Implementing Antimicrobial Stewardship Programs in Three Low- and Middle-income Country Tertiary Care Settings: Findings from a Multi-site Qualitative Study(2021) Rolfe, Jr, Robert JosephBackground: 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.
Item Open Access Emergence of Epidemic Dengue-1 Virus in the Southern Province of Sri Lanka.(PLoS Negl Trop Dis, 2016-10) Bodinayake, Champica K; Tillekeratne, L Gayani; Nagahawatte, Ajith; Devasiri, Vasantha; Kodikara Arachichi, Wasantha; Strouse, John J; Sessions, October M; Kurukulasooriya, Ruvini; Uehara, Anna; Howe, Shiqin; Ong, Xin Mei; Tan, Sharon; Chow, Angelia; Tummalapalli, Praveen; De Silva, Aruna D; Østbye, Truls; Woods, Christopher W; Gubler, Duane J; Reller, Megan EBACKGROUND: 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.Item Open Access First Point-Prevalence Study of Inpatient Antimicrobial Use in Five Public Hospitals in Southern Sri Lanka(2018) Sheng, TianchenObjectives
Inappropriate antimicrobial use is associated with adverse drug effects and antimicrobial resistance. Understanding prescribing practices is important for optimizing antimicrobial use. We investigated the prevalence, types, and indications for antimicrobials in Sri Lanka.
Methods
A point-prevalence study was conducted among inpatients at tertiary (1), secondary (1), and primary-level (3) public hospitals in Southern Province, Sri Lanka. From June-Aug 2017, all patients in medical, surgical, pediatric, and intensive care wards were included. Charts were assessed for systemic antibiotic, antifungal, and antiviral use in 1-day point-prevalence studies. Demographics, clinical characteristics, and antimicrobial use data were recorded from charts. Hospital and patient characteristics associated with antimicrobial therapy were assessed using the Chi-square test and Kruskall-Wallis tests. Potentially inappropriate antimicrobial use was defined as the receipt of two beta-lactam antibiotics or two antibiotics with activity against anaerobes or Pseudomonas aeruginosa.
Results
A total of 1,709 patients were included (69.6% tertiary, 21.7% secondary, and 8.7% primary). Patients were in medical (55.2%), surgical, (27.2%), pediatric (12.9%), and intensive care wards (4.7%). Overall, 54.7% (95% CI, 52.3%-57.1%) of patients were receiving antimicrobials. Antimicrobial use prevalence was similar across hospital type (p= 0.439), but varied by ward type: 43.1% in medical, 68.0% in surgical, 61.1% in pediatric, and 97.6% in intensive care wards (p<0.001). Commonly used antimicrobials were amoxicillin/clavulanate (33.8%), 3rd-generation cephalosporins (23.6%), metronidazole (16.6%), narrow and extended-spectrum penicillins (15.8%), clarithromycin (12.3%), 2nd-generation cephalosporins (10.7%), and carbapenems (10.4%). Common antimicrobial indications were lower respiratory infections (20.7%), soft tissue infections (9.4%), urinary tract infections (9.7%), and surgical prophylaxis (7.8%). Of patients receiving antimicrobials, potential inappropriate use was seen: 9.2% double anaerobic coverage, 7.6% double beta-lactam coverage, and 1.5% double P. aeruginosa coverage.
Conclusions
We report the first point-prevalence study of antimicrobial use in public hospitals in southern Sri Lanka. Over half of inpatients were receiving antimicrobials. High antimicrobial use and potentially inappropriate antimicrobial use should be addressed by future antimicrobial stewardship efforts.
Item Open Access Influenza Vaccination Implementation in Sri Lanka: A Cost-Effectiveness Analysis.(Vaccines, 2023-05) Neighbors, Coralei E; Myers, Evan R; Weerasinghe, Nayani P; Wijayaratne, Gaya B; Bodinayake, Champica K; Nagahawatte, Ajith; Tillekeratne, L Gayani; Woods, Christopher WInfluenza 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.Item Embargo Prevalence and Predictors of Antibiotic Prescription Among Patients Hospitalized with Viral Lower Respiratory Tract Infections in Southern Province, Sri Lanka(2023) Medrano, Perla GiselleBackground: Antimicrobial overprescription has been associated with antimicrobial resistance, and is common for lower respiratory tract infections (LRTI) as viral and bacterial infections generally present with similar clinical features. The aim of this study was to identify the prevalence and predictors of antibiotic prescription among children and adults hospitalized with viral LRTI. Methods: A prospective cohort study was conducted among patients hospitalized with viral LRTI in a tertiary care hospital in Southern Province, Sri Lanka from April 2018 to October 2021. Consecutive patients ≥1 year old who met a case definition for LRTI were enrolled. Patients’ demographic, clinical, and laboratory data were recorded. A nasopharyngeal sample and blood sample were collected from all patients for multiplex polymerase chain reaction (PCR) testing for respiratory pathogens and procalcitonin (PCT) detection, respectively. Among patients with viral RTI, demographic and clinical features associated with antibiotic prescription were identified using Chi Square and t-tests, as appropriate. Significant variables (p<0.05) on bivariable analyses were included in a multivariable logistic regression model to identify features associated with antibiotic prescription. The potential impact of procalcitonin testing on antibiotic prescription was simulated using standard PCT cut-offs. Analyses were conducted separately for children (<18 years) and adults using R Statistical Software (R Core Team 2022). Results: A total of 1217 patients were enrolled during the study period; of these, 438 (36.0%) had one or more respiratory viruses detected. Of 438 patients, 48.4% were male and 30.8% were children; the median age was 4 years (IQR 2-7) for children and 61 years (IQR 48-70) for adults. The most commonly detected viruses were influenza A (39.3%), human rhinovirus/ enterovirus (HRV/HEV; 28.3%), and respiratory syncytial virus A (RSV A; 10.3%). Overall, 114 (84.4%) children and 266 (87.8%) adults with respiratory viruses were treated with antibiotics during hospitalization. On multivariable modeling for children, neutrophil percentage (median 63.8% vs 47.3%, p=0.03) was positively associated with antibiotic prescription. Among adults, headache (60.6% vs 35.1%, p=0.003), presence of crepitations/crackles on exam (55.3% vs 21.6%, p<0.001), rhonchi/wheezing on exam (42.9% vs 18.9%, p=0.005), and presence of opacities on chest x-ray (27.4% vs 8.1%, p=0.01) were associated with antibiotic prescription. Access to PCT test results could have potentially decreased inappropriate antibiotic prescription in this study by 83.3%. Conclusions: A high percentage of viral detection and high prevalence of antibiotic prescription were observed among a large inpatient cohort with LRTI. Our results suggest that improved access to point-of-care biomarker testing may improve antimicrobial stewardship for LRTI in this low-resource setting.
Item Open Access Previously Derived Host Gene Expression Classifiers Identify Bacterial and Viral Etiologies of Acute Febrile Respiratory Illness in a South Asian Population.(Open forum infectious diseases, 2020-06) Tillekeratne, L Gayani; Suchindran, Sunil; Ko, Emily R; Petzold, Elizabeth A; Bodinayake, Champica K; Nagahawatte, Ajith; Devasiri, Vasantha; Kurukulasooriya, Ruvini; Nicholson, Bradly P; McClain, Micah T; Burke, Thomas W; Tsalik, Ephraim L; Henao, Ricardo; Ginsburg, Geoffrey S; Reller, Megan E; Woods, Christopher WBackground: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.Item Open Access Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection.(JAMA network open, 2022-04) Ko, Emily R; Henao, Ricardo; Frankey, Katherine; Petzold, Elizabeth A; Isner, Pamela D; Jaehne, Anja K; Allen, Nakia; Gardner-Gray, Jayna; Hurst, Gina; Pflaum-Carlson, Jacqueline; Jayaprakash, Namita; Rivers, Emanuel P; Wang, Henry; Ugalde, Irma; Amanullah, Siraj; Mercurio, Laura; Chun, Thomas H; May, Larissa; Hickey, Robert W; Lazarus, Jacob E; Gunaratne, Shauna H; Pallin, Daniel J; Jambaulikar, Guruprasad; Huckins, David S; Ampofo, Krow; Jhaveri, Ravi; Jiang, Yunyun; Komarow, Lauren; Evans, Scott R; Ginsburg, Geoffrey S; Tillekeratne, L Gayani; McClain, Micah T; Burke, Thomas W; Woods, Christopher W; Tsalik, Ephraim L; Antibacterial Resistance Leadership GroupImportance
Bacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacterial from viral infection in less than 1 hour may improve care and antimicrobial stewardship.Objective
To validate the host response bacterial/viral (HR-B/V) test and assess its ability to accurately differentiate bacterial from viral infection among patients with ARI.Design, setting, and participants
This prospective multicenter diagnostic study enrolled 755 children and adults with febrile ARI of 7 or fewer days' duration from 10 US emergency departments. Participants were enrolled from October 3, 2014, to September 1, 2019, followed by additional enrollment of patients with COVID-19 from March 20 to December 3, 2020. Clinical adjudication of enrolled participants identified 616 individuals as having bacterial or viral infection. The primary analysis cohort included 334 participants with high-confidence reference adjudications (based on adjudicator concordance and the presence of an identified pathogen confirmed by microbiological testing). A secondary analysis of the entire cohort of 616 participants included cases with low-confidence reference adjudications (based on adjudicator discordance or the absence of an identified pathogen in microbiological testing). Thirty-three participants with COVID-19 were included post hoc.Interventions
The HR-B/V test quantified the expression of 45 host messenger RNAs in approximately 45 minutes to derive a probability of bacterial infection.Main outcomes and measures
Performance characteristics for the HR-B/V test compared with clinical adjudication were reported as either bacterial or viral infection or categorized into 4 likelihood groups (viral very likely [probability score <0.19], viral likely [probability score of 0.19-0.40], bacterial likely [probability score of 0.41-0.73], and bacterial very likely [probability score >0.73]) and compared with procalcitonin measurement.Results
Among 755 enrolled participants, the median age was 26 years (IQR, 16-52 years); 360 participants (47.7%) were female, and 395 (52.3%) were male. A total of 13 participants (1.7%) were American Indian, 13 (1.7%) were Asian, 368 (48.7%) were Black, 131 (17.4%) were Hispanic, 3 (0.4%) were Native Hawaiian or Pacific Islander, 297 (39.3%) were White, and 60 (7.9%) were of unspecified race and/or ethnicity. In the primary analysis involving 334 participants, the HR-B/V test had sensitivity of 89.8% (95% CI, 77.8%-96.2%), specificity of 82.1% (95% CI, 77.4%-86.6%), and a negative predictive value (NPV) of 97.9% (95% CI, 95.3%-99.1%) for bacterial infection. In comparison, the sensitivity of procalcitonin measurement was 28.6% (95% CI, 16.2%-40.9%; P < .001), the specificity was 87.0% (95% CI, 82.7%-90.7%; P = .006), and the NPV was 87.6% (95% CI, 85.5%-89.5%; P < .001). When stratified into likelihood groups, the HR-B/V test had an NPV of 98.9% (95% CI, 96.1%-100%) for bacterial infection in the viral very likely group and a positive predictive value of 63.4% (95% CI, 47.2%-77.9%) for bacterial infection in the bacterial very likely group. The HR-B/V test correctly identified 30 of 33 participants (90.9%) with acute COVID-19 as having a viral infection.Conclusions and relevance
In this study, the HR-B/V test accurately discriminated bacterial from viral infection among patients with febrile ARI and was superior to procalcitonin measurement. The findings suggest that an accurate point-of-need host response test with high NPV may offer an opportunity to improve antibiotic stewardship and patient outcomes.Item Open Access RADx-UP Testing Core: Access to COVID-19 Diagnostics in Community-Engaged Research with Underserved Populations.(Journal of clinical microbiology, 2023-08) Narayanasamy, Shanti; Veldman, Timothy H; Lee, Mark J; Glover, William A; Tillekeratne, L Gayani; Neighbors, Coralei E; Harper, Barrie; Raghavan, Vidya; Kennedy, Scott W; Carper, Miranda; Denny, Thomas; Tsalik, Ephraim L; Reller, Megan E; Kibbe, Warren A; Corbie, Giselle; Cohen-Wolkowiez, Michael; Woods, Christopher W; Petti, Cathy AResearch on the COVID-19 pandemic revealed a disproportionate burden of COVID-19 infection and death among underserved populations and exposed low rates of SARS-CoV-2 testing in these communities. A landmark National Institutes of Health (NIH) funding initiative, the Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) program, was developed to address the research gap in understanding the adoption of COVID-19 testing in underserved populations. This program is the single largest investment in health disparities and community-engaged research in the history of the NIH. The RADx-UP Testing Core (TC) provides community-based investigators with essential scientific expertise and guidance on COVID-19 diagnostics. This commentary describes the first 2 years of the TC's experience, highlighting the challenges faced and insights gained to safely and effectively deploy large-scale diagnostics for community-initiated research in underserved populations during a pandemic. The success of RADx-UP shows that community-based research to increase access and uptake of testing among underserved populations can be accomplished during a pandemic with tools, resources, and multidisciplinary expertise provided by a centralized testing-specific coordinating center. We developed adaptive tools to support individual testing strategies and frameworks for these diverse studies and ensured continuous monitoring of testing strategies and use of study data. In a rapidly evolving setting of tremendous uncertainty, the TC provided essential and real-time technical expertise to support safe, effective, and adaptive testing. The lessons learned go beyond this pandemic and can serve as a framework for rapid deployment of testing in response to future crises, especially when populations are affected inequitably.Item Open Access Streptococcus Pneumoniae Colonization among Children in Galle, Sri Lanka: A Cross-Sectional Study(2020) Zhang, ChiBackground: Streptococcus pneumoniae, a Gram-positive bacterium that is found in the human respiratory tract, is the most common cause of bacterial pneumonia globally. Pneumococcal pneumonia can be effectively prevented by administering pneumococcal vaccines but pneumococcal vaccination is not provided through the public healthcare sector in Sri Lanka at present. This study will serve as evidence instructing future decisions regarding the utility of vaccination.
Methods: A cross-sectional survey was conducted in Galle, Sri Lanka from July to September 2019 . Eleven Medical Officer of Health (MOH) clinics, which provide routine vaccinations to infants and children through the public health sector, were selected as the study setting. The parents of consecutive children ≤5 years of age were approached for consent. A nasopharyngeal sample was collected from each enrolled child and socio-demographic and clinical data were obtained by interviewing the parents. Routine microbiological testing was conducted to confirm the presence of S. pneumoniae isolates. Antibiotic susceptibility testing was performed on confirmed isolates using Kirby-Bauer disc diffusion. Sociodemographic and clinical characteristics associated with S. pneumoniae colonization were assessed using bivariable and multivariable logistic regression in R.
Results: Among 123 enrolled patients, 26 (21.1%) were found to be colonized with S. pneumoniae. Higher risk of S. pneumoniae colonization was found to be associated with living with other children <5 years (Unadjusted OR=4.58, 95%CI: 1.69-12.83); Adjusted OR=3.99, 95%CI: 1.19-13.39) in both bivariate and multivariate analysis. With age >2 years was found to be associated with lower risk of being infected (Unadjusted OR=0.19, 95%CI: 0.02-0.84) in bivariate analysis, and drinking boiled water was found protective to the carriage than no treatment (Adjusted OR=0.11, 95%CI: 0.02-0.65) in multivariate analysis. For antibiotic resistance, the non-susceptible prevalence was 94.4% to oxacillin/penicillin, 72.2% to erythromycin, and 44.4% to clindamycin. All isolates were susceptible to levofloxacin.
Discussion: This is the first report of S. pneumoniae colonization prevalence among children in Southern Province, Sri Lanka. One-fifth of children were found to be colonized with S. pneumoniae, and oxacillin non-susceptibility prevalence was high. Further characterization must be performed to identify serotypes of colonizing strains and to correlate with serotypes present in available vaccines. Our results provide evidence regarding burden of pneumococcal colonization in Sri Lanka, and may help guide pneumococcal vaccine decisions in Sri Lanka.
Item Open Access The Epidemiology, Risk Profiles, and Outcomes of Patients Infected with Carbapenem-Resistant Gram-Negative Bacterial Infections(2020) Bollinger, JohnBackground: Antimicrobial resistance (AMR) is a major public health problem that threatens economic security, puts health at risk, and jeopardizes global progress towards the Millennium Development Goals (MDGs) and Sustainable Development Goals (SDGs). Limited data exist regarding risk factors, health outcomes, and treatment of carbapenem-resistant gram-negative bacteria (GNB) infections in Sri Lanka. The purpose of this study was to describe the epidemiology, risk factors, and outcomes among patients with infections due to carbapenem-resistant GNB. Methods: The study was conducted at Teaching Hospital Karapitiya (THK), the largest tertiary care hospital in the Southern Province of Sri Lanka from September 2019 through January 2020. The study population consisted of inpatients at THK. Laboratory-based surveillance was performed using routine clinical samples received by the clinical microbiology laboratory at THK to identify cases (carbapenem-resistant gram-negative isolates) and controls (carbapenem-susceptible gram-negative isolates) for case-control analysis. Three groups of GNB isolates were included in the study: Enterobacteriaceae, Pseudomonas spp., and Acinetobacter spp. Prevalence of carbapenem resistance was calculated, and risk factors were assessed for association with resistance by logistic regression. Results: A total of 474 gram-negative bacterial isolates were screened for complete antibiotic susceptibility data at THK from October 2019 to November 2019. In total, 28.3% of Enterobacteriaceae isolates, 21.7% of Pseudomonas spp., and 66.7% ofAcinetobacter spp. exhibited carbapenem resistance. None of the sociodemographic or clinical factors explored was significantly associated with having a carbapenem-resistant isolate. Conclusions: Overall, a high prevalence of carbapenem resistance was noted. The present data justify the need for antimicrobial stewardship programs and the implementation of consistent surveillance. While these data do not identify risk factors associated with carbapenem resistance, future research should further explore potential risk factors specific to the Sri Lankan context.
Item Open Access The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood.(Frontiers in immunology, 2021-01) Tsalik, Ephraim L; Fiorino, Cassandra; Aqeel, Ammara; Liu, Yiling; Henao, Ricardo; Ko, Emily R; Burke, Thomas W; Reller, Megan E; Bodinayake, Champica K; Nagahawatte, Ajith; Arachchi, Wasantha K; Devasiri, Vasantha; Kurukulasooriya, Ruvini; McClain, Micah T; Woods, Christopher W; Ginsburg, Geoffrey S; Tillekeratne, L Gayani; Schughart, KlausViruses 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.