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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 β-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.

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.

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.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.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.The HR-B/V test quantified the expression of 45 host messenger RNAs in approximately 45 minutes to derive a probability of bacterial infection.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 score0.19], viral likely [probability score of 0.19-0.40], bacterial likely [probability score of 0.41-0.73], and bacterial very likely [probability score0.73]) and compared with procalcitonin measurement.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.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.

This cross-sectional study aimed to assess HIV-related knowledge and attitudes of PHMs, the frontline community health workers in Sri Lanka. Two-hundred and ninety-one PHMs were recruited. PHMs’ knowledge level was good (79.9% of answers were correct) but could be improved. Those more knowledgeable about HIV and with higher education demonstrated a more positive attitude toward PLWH. A more negative attitude, less training and older age were associated with having a stronger intention to engage in extra precautionary behaviors. PHMs need further HIV training to improve their knowledge to better educate the community. By reducing PHMs misperceptions about HIV, they may develop a more positive attitude and thus help reduce the general public’s stigma associated with PLWH. Keywords: HIV, PLWH, Stigma, attitude, community health workers, midwives, Asia, Sri Lanka

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.

Background Mass drug administration (MDA) is a strategy to improve health at the population level through widespread delivery of medicine in a community. We surveyed the literature to summarize the benefits and potential risks associated with MDA of antibacterials, focusing predominantly on azithromycin as it has the greatest evidence base. Main body High-quality evidence from randomized controlled trials (RCTs) indicate that MDA-azithromycin is effective in reducing the prevalence of infection due to yaws and trachoma. In addition, RCTs suggest that MDA-azithromycin reduces under-five mortality in certain low-resource settings that have high childhood mortality rates at baseline. This reduction in mortality appears to be sustained over time with twice-yearly MDA-azithromycin, with the greatest effect observed in children Conclusions Evidence shows that MDA-azithromycin programs may be beneficial for reducing trachoma, yaws, and mortality in children Graphical Abstract

Coagulase-negative staphylococci (CoNS) are considered the most common cause of nosocomial bloodstream infections; yet, these species are frequently designated as contaminants in the absence of systemic signs and symptoms of infection. Immunocompromised patients or those with prosthetic devices are at increased risk for clinically significant bacteremia. With the advent of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) in clinical practice, there has been improved specificity of CoNS isolate identification and further elucidation of underrecognized pathogenic species. Staphylococcus pettenkoferi was a novel CoNS species first identified in 2002 and thought to be misdiagnosed as other CoNS due to limitations in biochemical identification. There is increasing identification of S. pettenkoferi isolates; however, there are limited case reports of clinically significant S. pettenkoferi bacteremia and no reported cases within the United States. We present the first known case of S. pettenkoferi from an American intensive care unit.

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.

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.

Additional file 1: Supplementary file 1. OPD pre- and post-visit questionnaires. English version pre- and post-visit study questionnaires.

Additional file 1: Table S1. Description of mothers at enrollment and reassessment in addition to bivariable analysis of risk factors associated with intestinal colonization with multidrug resistant Enterobacteriaceae (MDRE). Table S2. Sensitivity analysis for definition of isolates that were not re-culturable. Table S3. Summary of antibiotic resistance by phenotypic susceptibility testing of isolates found in mothers and infants. Table S4. Summary of antibiotic resistance-encoding genes present in isolates found in mothers and infants. Table S5. Information on E. coli isolates characterized using whole genome sequencing. Table S6. Mothers’ isolates categorized by phylogroup and Multilocus Sequence Typing (MLST). Table S7. Infants’ isolates categorized by phylogroup and Multilocus Sequence Typing (MLST).

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., Host biomarkers can identify bacterial versus viral acute respiratory infection (ARI). Previously, we derived host gene expression classifiers that accurately identify bacterial versus viral ARI. Here, we show that our classifiers had high predictive accuracy in a South Asian cohort.

Background Antimicrobial stewardship programs (ASPs) are being developed internationally to mitigate the misuse of antimicrobials. An understanding of current practices and prescribing patterns is necessary to determine targets to develop context-specific ASPs in low- and middle-income country (LMIC) hospitals. Methods We conducted a prospective study of patients admitted to the adult medical wards at three LMIC tertiary care centers in 2018- 2019: a 1,800-bed public hospital in Galle, Sri Lanka; a 991-bed public hospital in Eldoret, Kenya; and a 630-bed private hospital in Moshi, Tanzania. Information regarding antimicrobial therapy received during hospitalization, indications for antimicrobial therapy, and duration of antimicrobial use were extracted from the medical record. Results In total, 3150 patients were enrolled: 1297 in Sri Lanka, 750 in Kenya, and 1103 in Tanzania. Antimicrobial use prevalence varied between the three sites, with 56.0% of patients receiving antimicrobials during hospitalization in Sri Lanka, 56.5% in Kenya, and 35.4% in Tanzania. Third-generation cephalosporins were used most frequently in Kenya (70.0%) and Tanzania (73.1%), whereas amoxicillin/ clavulanic acid was used most frequently in Sri Lanka (48.4%). Lower respiratory tract infection was the most common indication for antimicrobial use in all three locations: 37.4% in Sri Lanka, 27.8% in Kenya, and 49.2% in Tanzania. No clear indication for antimicrobial use was documented among 11.6% patients receiving antimicrobials in Sri Lanka, 32.8% in Kenya, and 10.5% in Tanzania. In Tanzania, 8.6% of the patients had documentation of input from the microbiology or infectious diseases teams compared to less than 1% in either Sri Lanka or Kenya. Pertinent culture data related to the primary indication for antimicrobials was present in 16.1% (Sri Lanka), 6.1% (Kenya), and 7.4% (Tanzania). Conclusion Unclear documentation for antimicrobial use was common in all three sites and most patients on antimicrobial therapy did not have pertinent culture data. Improving documentation and the capacity of the local microbiology laboratories could be initial targets for ASPs in these LMIC hospitals. Disclosures All Authors: No reported disclosures

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.

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.

Leprosy is caused by the Mycobacterium leprae bacillus. Pockets of high endemicity remain in a number of countries including Sri Lanka, in spite of the fact that elimination has been achieved at the national level. In 2012, in a village in the Puttlam district, dermatologists reported an increase in individuals with leprosy. This village had been established in the 1990s for people displaced from Northern Sri Lanka during a civil war. A comprehensive household survey was conducted by district health officials from June to July 2012, and all household members present during the survey period were examined for leprosy lesions. Patients with suspected leprosy were referred to a dermatology clinic for clinical or pathological confirmation. The prevalence of leprosy was high (511 per 10 000 population). Household contact with another patient with leprosy increased the risk of leprosy (odds ratio = 6.69; P < .001). Continued vigilance is needed to keep leprosy at bay in high-risk communities.

ObjectivesTo determine aetiology of illness among children and adults presenting during outbreak of severe respiratory illness in Southern Province, Sri Lanka, in 2018.DesignProspective, cross-sectional study.Setting1600-bed, public, tertiary care hospital in Southern Province, Sri Lanka.Participants410 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.ResultsWe 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.ConclusionsThis 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.

Background: Rubber production is an important component of the Sri Lankan economy. Prior reports have raised concerns about poverty and poor physical and social living conditions among rubber tappers. Objective: To assess rubber tappers’ psychological health and distress. Methods and Material: A cross-sectional survey was conducted among 300 rubber tappers in two large rubber plantations in southern Sri Lanka from September to November 2014. Structured questionnaires including the Peradeniya Depression Scale (PDS) and the 10-item Perceived Stress Scale (PSS-10) were administered. The prevalences of depression and stress were calculated, including across sociodemographic and work history variables of interest. Results: Each plantation contributed 150 of the 300 participants. The majority were women (n = 183, 61%) with a median age of 47 years (range 21 to 89). Based on the PDS, 9% of the rubber tappers screened positive for depression. While on the PSS-10, 10% demonstrated a high level of perceived stress. On log-binomial regression, persons who were widowed, divorced, or separated compared to being married had a higher prevalence of depression and high stress. A higher prevalence of stress was found in Tamil versus Sinhalese as well as Christian versus Buddhist participants. A higher prevalence of depression was seen in workers with over 30 years of experience compared to less experienced counterparts. Conclusions: Depression was more common in rubber tappers in this study than among other non-plantation Sri Lankan populations. Further research is needed to elucidate factors associated with psychological distress and to foster support mechanisms for the rubber tappers.

Background Antimicrobial stewardship programs (ASPs) have been shown to improve the appropriate use of antimicrobials, especially in high-income countries. However, ASPs are relatively less well implemented in low-or-middle income countries. To improve the effectiveness of ASPs in these settings, it is important to determine the core actions and targets for improving antimicrobial use. We sought to describe the prevalence and patterns of antibiotic use at a tertiary care hospital in Tanzania. Methods Consecutive patients admitted to an adult medical ward at a tertiary care hospital, Kilimanjaro Christian Medical Centre, in Moshi, Tanzania were enrolled from June 2018 to March 2019. The medical record was reviewed for data regarding the type of antibiotics prescribed, indications for use, and microbiologic testing ordered. Results A total of 1103 patients were enrolled during the study period. The majority of patients were males (663, 60.1%), with the median age being 54 years (IQR 39–70). About one-third (390, 35.4%) of the admitted patients received antimicrobials during hospitalization, with pneumonia being the leading indication for antimicrobial use (158, 40.5%). The most commonly used antibiotics included ceftriaxone in 285 (73.1%), metronidazole in 155 (39.7%), and amoxicillin/ ampicillin in 46 (11.8%) patients. The median duration of antimicrobial use was 5 days (IQR 3–7). Few patients on antimicrobials (27, 6.9%) had culture results, of which half (15, 55.6%) were positive for an organism and a minority (8, 29.6%) were susceptible to the antibiotics being used. Overall, mortality in the cohort was 22.7% and the median duration of hospitalization was 5 days (IQR 3–8). Conclusion Antibiotics were used in a substantial proportion of admitted patients. However, in most cases, treatment was empirical with limited use of culture results. Future ASP efforts can target the improved use of microbiologic cultures to target antimicrobial use. Disclosures All authors: No reported disclosures.

Background Skin and soft-tissue infections (SSTI) are a common reason for antimicrobial use in the outpatient and inpatient settings. Inappropriate antimicrobial use for SSTI is common. We determined the prevalence of SSTI and associated inappropriate antimicrobial use among inpatients in Sri Lanka. Methods A point-prevalence study of antimicrobial use was conducted using one-day cross-sectional surveys at five public hospitals in Southern Province, Sri Lanka from Jun-August 2017. Inpatients’ medical records were reviewed for clinical data including antimicrobials prescribed. Inappropriate antimicrobial use was identified as (1) antimicrobial use discordant with guidelines by the Sri Lanka College of Microbiologists (SLCM), and (2) redundant combinations of antimicrobials. Results Of 1,709 surveyed patients, 935 (54.7%) received antimicrobials, of whom 779 (83.3%) had a specified or inferred indication for antimicrobial use. Among patients with an indication for antimicrobial use, SSTI was the second leading indication (181 patients, 23.2%) after lower respiratory tract infection (194, 24.9%). One-third (62, 34.2%) of patients with SSTI had a history of diabetes. Commonly used antimicrobials for SSTI included amoxicillin and clavulanic acid (40.3%), extended-spectrum penicillins (24.9%), and metronidazole (22.1%). inappropriate antimicrobial use was observed in 53.0% of SSTI patients, with redundant antibiotic therapy in 35.9% and antimicrobials discordant with SLCM guidelines in 32.6%. Conclusion SSTI was a common reason for antimicrobial use among inpatients in Sri Lanka, with more than half of patients receiving potentially inappropriate antimicrobial therapy. We identified targets for future antimicrobial stewardship efforts. Disclosures All authors: No reported disclosures.

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.

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.

Health care-associated infections such as catheter-associated urinary tract infections (CAUTIs) are prevalent in resource-limited settings. This study was carried out to determine whether a multifaceted intervention targeting health care personnel would reduce CAUTI rates in a public hospital located in a resource-limited setting.A one group, pretest-posttest study was carried out from March to July 2012 in a public district hospital in Nairobi, Kenya. Patients admitted to adult medical wards, and who received urinary catheters, were evaluated for symptomatic CAUTIs using a modified definition by the Centers for Disease Control and Prevention. After collecting baseline CAUTI rates for 8 weeks, a multifaceted intervention consisting of lectures, reminder signs, and infection prevention rounds (week 9) was implemented. The postintervention rate of CAUTIs was measured over 7 subsequent weeks. Bivariable analysis was performed to determine whether the intervention was associated with reduced CAUTIs.A total of 125 patients received urinary catheters, with 82 preintervention and 43 postintervention. Mean duration of catheterization did not change between phases (6.9 vs 5.6 days, respectively, P = .322), but catheter utilization ratio decreased from 0.14 to 0.09 (P.001). There were 13 preintervention CAUTIs (for 30.4 infections per 1,000 catheter-days) and no postintervention CAUTIs (P = .002).In this resource-limited setting, the baseline rate of CAUTIs was high. A low-cost, multifaceted intervention resulted in decreased urinary catheter use and CAUTI rates.

Background The global emergence of antimicrobial resistance poses a major public health threat. However, there are little data regarding antimicrobial use from many low- or middle-income countries. In this study, we determined the prevalence and patterns of antibiotic prescription among outpatients at a tertiary healthcare facility in Sri Lanka. Methods The study was conducted at the Outpatient Department (OPD) of the largest public tertiary care center in Southern Province, Sri Lanka. This is a free walk-in clinic serving upwards of 1,000 patients per day. Adult and pediatric OPD patients were recruited for a cross-sectional survey in February–April 2019. Pre-visit and post-visit questionnaires were verbally administered to obtain information regarding participants’ demographics and presenting illness. The OPD pharmacy’s electronic prescribing system was queried to calculate the prevalence of antibiotic prescriptions among enrolled patients. Logistic regression was performed to identify features associated with antibiotic prescription. Results Of 408 patients surveyed, 246 (62.9%) were female and 88 (21.7%) were children Conclusion We show a high prevalence of outpatient antibiotic prescription despite limited diagnostic evaluation at a tertiary medical facility in Southern Province, Sri Lanka. Antibiotic stewardship efforts, especially targeting respiratory illness, may help improve antibiotic use in this setting. Disclosures All authors: No reported disclosures.

Background Antibiotic resistance is an emerging global public health threat with inappropriate use of antibiotics as one of the major drivers. In Sri Lanka, antibiotic consumption is increasing, while little is known about how patients perceive antibiotics. We conducted a qualitative study to better understand patients’ knowledge, perceptions, and attitudes toward antibiotics. Methods Semi-structured interviews were conducted in the local language (Sinhala) and audio recorded for 18 patients with lower respiratory tract infections (LRTI) admitted to a large, public tertiary care hospital in southern Sri Lanka. Interviews were transcribed and then translated into English. Translated interviews were analyzed for themes regarding care-seeking behavior, patients’ knowledge of disease etiology and treatment of LRTI. Results Almost all patients mentioned multiple care visits and polypharmacy prior to admission. When seeking care, patients mainly focused on finding a quick cure, mostly by visiting several different private physicians. However, self-medication was also common. Patients reused prescriptions for antibiotics, kept antibiotics for later use after prematurely stopping their course of treatment and bought antibiotics over-the-counter. Patients’ knowledge of disease etiology and antibiotics was poor. Most patients described non-microbial causes such as exposure to dust and cold weather for their illness. Only a few patients were aware of antibiotic resistance. Despite the desire to receive more information regarding disease and treatment, transfer of information between patients and physicians was limited and mainly confined to prescription instructions. Conclusion This qualitative study in Sri Lanka suggests inappropriate use of antibiotics is a multifactorial problem. Patients’ poor knowledge of disease and treatment, poor information transfer between physicians and patients, high demand for medicines, overprescribing by physicians, and self-medication were found as possible obstructive factors to improve antibiotic usage. To improve antibiotic use, a multifaceted approach is needed with improvement of awareness by patients, public, and physicians regarding antibiotic use and antibiotic resistance. Disclosures All authors: No reported disclosures.

BackgroundAcute 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.MethodsWe 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.ResultsStandard 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 ConclusionClinical prediction tools and targeted rapid influenza testing may be cost-saving strategies in Sri Lanka when accounting for the societal cost of antimicrobial resistance.

BACKGROUND Extended-spectrum s-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 s-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 s-lactamase. Further epidemiologic studies of infections due to ESBL-PE are urgently needed to better prevent and treat these infections in South Asia.

Background Acute febrile illness is a frequent cause of hospitalization in the tropics and often presents with respiratory symptoms, even when caused by nonrespiratory pathogens. Previously, host-based gene expression signatures accurately identified acute respiratory infections as being bacterial or viral in a U.S. cohort. We determined signature performance in a Sri Lankan cohort with acute febrile respiratory illness (AFRI). Methods We enrolled patients with AFRI in Sri Lanka from July 2012 to May 2013 and collected nasopharygeal swabs, acute/ convalescent sera, and blood in PAXgene RNA tubes. Bacterial (Orientia tsutsugamushi, Leptospira spp.) and viral (influenza A/B, dengue) infections were confirmed using polymerase chain reaction, virus isolation, enzyme immunoassay, and/or microscopic agglutination testing. We extracted total RNA and performed host RNA sequencing (Illumina). We aligned reads to hg38 reference genome using Bowtie2, quantified at isoform level using Express version 1.5.1, and normalized using trimmed-mean normalization. The original model estimated three classes and separate signatures predicted bacterial infections, viral infections, and non-infectious illnesses. Regularized regression was used to predict bacterial and viral infections based on prior signatures. Accuracy was estimated using leave-one-out cross-validation. Results Among 43 patients with viral infections (14 dengue, 29 influenza) and 16 patients with bacterial infections (six Leptospira spp., 10 O. tsutsumagushi), median age was 37 years (IQR 23–51) and 49% were male. Of five respiratory symptoms (cough, sore throat, rhinitis/ congestion, shortness of breath, and pain with breathing), median (IQR) number of symptoms was 2 (1–2) for influenza, 2 (1–2) for dengue, 2 (2–3) for Leptospira spp., and 1.5 (1–2) for O. tsutsumagushi. We observed high predictive accuracy in discriminating bacterial and viral infections: AUROC 0.91 for the bacterial and AUROC 0.81 for the viral model. At enrollment, 65% of viral and 50% of bacterial AFRI patients received antibiotics. Conclusion Host gene expression classifiers performed well in a Sri Lankan population with AFRI, even with nonrespiratory pathogens that may not be readily identified. Host-based diagnostics may play a critical role in improving diagnostic ability and antibiotic use globally. Disclosures E. L. Tsalik, Host Response, Inc.: Founder, Equity. G. S. Ginsburg, Host Response Inc.: Board Member, Founder, Scientific Advisor and Shareholder, Stock (currently worth

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., Author summary Dengue is an important cause of acute fever in the tropics that is difficult to distinguish from other common etiologies of fever. The World Health Organization (WHO) revised criteria for the clinical diagnosis and classification of acute dengue in 2009. The performance of these criteria has not been widely evaluated in countries where dengue is endemic. We confirmed acute dengue in 388 of 976 patients presenting with acute febrile illness (AFI) to the largest tertiary care center in the Southern Province of Sri Lanka. We found specific clinical features and laboratory investigations to be predictive of acute dengue versus other AFI. The new WHO 2009 classification was more sensitive than physicians’ clinical diagnosis for identification of acute dengue on admission to hospital, but also over-estimated the severity of illness. Further large cohort studies are warranted to validate the performance of the 2009 WHO criteria for diagnosis and prognosis of dengue in regions where the disease burden is high.

The World Health Organization (WHO) has recommended the use of clinical staging alone and with total lymphocyte count to identify HIV infected children in need of antiretroviral therapy (ART) in resource-limited settings, when CD4 cell count is not available.We prospectively enrolled children obtaining care for HIV infection at the Kilimanjaro Christian Medical Centre Pediatric Infectious Diseases Clinic in Moshi, Tanzania between March 2004 and May 2006 for this cohort study.One hundred ninety two (89.7%) of 214 children met WHO ART initiation criteria based on clinical staging or CD4 cell count. Several low-cost measures identified individuals who met WHO ART initiation criteria to the following degree: WHO stages 3 or 4 had 87.5% (95% CI, 82.8-92.1) sensitivity and, by definition, 100% (CI, 100-100) specificity; WHO recommended advance disease TLC cutoffs: sensitivity = 23.9% (95% CI, 17.3-30.5) specificity = 78.2% (95% CI, 67.3-89.1). Low TLC was a common finding, (50 of 214; 23%); however, it did not improve the sensitivity or specificity of clinical staging in identifying the severely immunosuppressed stage 2 children. Growth failure or use of total lymphocyte counts in isolation were not reliable indicators of severe immunosuppression or need to initiate ART.The use of total lymphocyte count does not improve the ability to identify children in need of ART compared with clinical staging alone. Low absolute lymphocyte count did not correlate with severe immunosuppression based on CD4 cell count in this cohort.

Acute respiratory tract infections (ARTIs) are a common reason for unnecessary antibiotic prescriptions worldwide. Our objective was to determine if providing access to rapid influenza test results could reduce antibiotic prescriptions for ARTIs in a resource-limited setting. We conducted a prospective, pre-post study from March 2013 to October 2014. Outpatients presenting to a hospital in Sri Lanka were surveyed for influenza-like illness-onset of fever ≥ 38.0°C and cough in prior 7 days. Enrolled patients were administered a structured questionnaire, physical examination, and nasal/nasopharyngeal sampling for rapid influenza A/B testing. Influenza test results were released only during phase 2 (January-October 2014). We enrolled 571 patients with ILI-316 in phase 1 and 241 in phase 2. The proportion positive for influenza was 46.5% in phase 1 and 28.6% in phase 2, P < 0.001. Between phases, antibiotic prescriptions decreased from 81.3% to 69.3% (P = 0.001) among all patients and from 83.7% to 62.3% (P = 0.001) among influenza-positive patients. On multivariable analysis, a positive influenza result during phase 2 was associated with lower odds of antibiotic prescriptions (OR = 0.50, 95% CI = 0.26-0.95). This prospective study suggests that providing access to rapid influenza testing may reduce unnecessary antibiotic prescriptions in resource-limited settings.

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., Author Summary Dengue is a globally emerging cause of fever that is caused by four serotypes of virus (DENV1-4). Since the 1960s, dengue in Sri Lanka has been documented primarily along the heavily urbanized western coast. Outbreaks from 2005–2008 were attributed to a new type of DENV-3 and more recently to a newly introduced type of DENV-1. Having identified serotypes other than DENV-1 as an important cause of fever in southern Sri Lanka in 2007, our prospective surveillance in 2012 enabled detection and characterization of an epidemic of dengue that caused 388 (39.8%) hospitalizations for fever. DENV-1 accounted for 91.2% of 351 virologically confirmed cases; isolates were most closely related to sequences described from China and Southeast Asia, not nearby India. Acute dengue was associated with self-reported rural residence, travel, and rainfall. Emergence of DENV-1 as the foremost serotype in the densely populated but agrarian southern Sri Lanka highlights the changing epidemiology of dengue and need for continued surveillance and prevention.

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.