Infections In Febrile Children Research Articles

Evaluation of a Novel Point-of-Care Blood Myxovirus Resistance Protein A Measurement for the Detection of Viral Infection at the Pediatric Emergency Department.

Prompt differentiation of viral from bacterial infections in febrile children is pivotal in reducing antibiotic overuse. Myxovirus resistance protein A (MxA) is a promising viral biomarker. We evaluated the accuracy of a point-of-care (POC) measurement for blood MxA level compared to the reference enzyme immunoassay in 228 febrile children aged between 4 weeks and 16 years, enrolled primarily at the emergency department (ED). Furthermore, we analyzed the ability of MxA to differentiate viral from bacterial infections. The mean difference between POC and reference MxA level was -76 µg/L (95% limits of agreement from -409 to 257 µg/L). Using a cutoff of 200 µg/L, POC results were uniform with the reference assay in 199 (87.3%) children. In ED-collected samples, the median POC MxA levels (interquartile range) were 571 [240-955] µg/L in children with viral infections, 555 (103-889) µg/L in children with viral-bacterial co-infections, and 25 (25-54) µg/L in children with bacterial infections (P < 0.001). MxA cutoff of 101 µg/L differentiated between viral and bacterial infections with 92% sensitivity and 91% specificity. POC MxA measurement demonstrated acceptable analytical accuracy compared to the reference method, and good diagnostic accuracy as a biomarker for viral infections.

Prevalent Bacterial Etiologies of Urinary Tract Infections in Febrile Children Under Five Years of at Federal Medical Centre, Owerri, Imo State, Nigeria

Urinary Tract Infections (UTIs) in children under five years old pose a significant health concern, influenced by various factors like bacterial agents, anatomy, immunity, and genetics. The study aimed to identify prevalent bacterial causes of UTIs in febrile children under five at a medical center in Nigeria. Among 170 participants, E. coli was the most frequently isolated bacteria (37.5%), followed by Klebsiella spp (18.8%) and Staphylococcus aureus (15.6%). The research underscores E. coli as the primary uropathogen, aligning with global trends, while acknowledging local variations in UTI causative agents. Keywords: Urinary Tract Infections, Febrile Children, Bacterial Etiologies and Pediatric UTI.

Evaluating the Predictive Efficacy of Dipstick Urinalysis for Detecting Urinary Tract Infections in Febrile Children Under Five Years of Age at Federal Medical Centre, Owerri, Imo State, Nigeria

This study aimed to assess the predictive efficacy of dipstick urinalysis in detecting urinary tract infections (UTI) among febrile children under five years of age at the Federal Medical Centre, Owerri, Imo State, Nigeria. The research involved a hospital-based descriptive cross-sectional study, analyzing the diagnostic performance of nitrite and leucocyte esterase tests on urine dipsticks. The results revealed low sensitivity but high specificity for both tests, suggesting their potential role in excluding UTI. The findings emphasize the importance of combining dipstick urinalysis with urine culture for accurate diagnosis in febrile children. Keywords: Urinary tract infections, Dipstick urinalysis, Febrile children, Nitrite, Leucocyte esterase, Diagnostic efficacy, Nigeria.

Evaluating the Predictive Efficacy of Dipstick Urinalysis for Detecting Urinary Tract Infections in Febrile Children Under Five Years of Age at Federal Medical Centre, Owerri, Imo State, Nigeria

This study aimed to assess the predictive efficacy of dipstick urinalysis in detecting urinary tract infections (UTI) among febrile children under five years of age at the Federal Medical Centre, Owerri, Imo State, Nigeria. The research involved a hospital-based descriptive cross-sectional study, analyzing the diagnostic performance of nitrite and leucocyte esterase tests on urine dipsticks. The results revealed low sensitivity but high specificity for both tests, suggesting their potential role in excluding UTI. The findings emphasize the importance of combining dipstick urinalysis with urine culture for accurate diagnosis in febrile children. Keywords: Urinary tract infections, Dipstick urinalysis, Febrile children, Nitrite, Leucocyte esterase, Diagnostic efficacy, Nigeria

Clinical and Microbiological Profiles of Urinary Tract Infections in Febrile Children Aged Six Months to Five Years Attending a Tertiary Care Hospital in India

Clinical and Microbiological Profiles of Urinary Tract Infections in Febrile Children Aged Six Months to Five Years Attending a Tertiary Care Hospital in India

A multi-platform approach to identify a blood-based host protein signature for distinguishing between bacterial and viral infections in febrile children (PERFORM): a multi-cohort machine learning study

Differentiating between self-resolving viral infections and bacterial infections in children who are febrile is a common challenge, causing difficulties in identifying which individuals require antibiotics. Studying the host response to infection can provide useful insights and can lead to the identification of biomarkers of infection with diagnostic potential. This study aimed to identify host protein biomarkers for future development into an accurate, rapid point-of-care test that can distinguish between bacterial and viral infections, by recruiting children presenting to health-care settings with fever or a history of fever in the previous 72 h. In this multi-cohort machine learning study, patient data were taken from EUCLIDS, the Swiss Pediatric Sepsis study, the GENDRES study, and the PERFORM study, which were all based in Europe. We generated three high-dimensional proteomic datasets (SomaScan and two via liquid chromatography tandem mass spectrometry, referred to as MS-A and MS-B) using targeted and untargeted platforms (SomaScan and liquid chromatography mass spectrometry). Protein biomarkers were then shortlisted using differential abundance analysis, feature selection using forward selection-partial least squares (FS-PLS; 100 iterations), along with a literature search. Identified proteins were tested with Luminex and ELISA and iterative FS-PLS was done again (25 iterations) on the Luminex results alone, and the Luminex and ELISA results together. A sparse protein signature for distinguishing between bacterial and viral infections was identified from the selected proteins. The performance of this signature was finally tested using Luminex assays and by calculating disease risk scores. 376 children provided serum or plasma samples for use in the discovery of protein biomarkers. 79 serum samples were collected for the generation of the SomaScan dataset, 147 plasma samples for the MS-A dataset, and 150 plasma samples for the MS-B dataset. Differential abundance analysis, and the first round of feature selection using FS-PLS identified 35 protein biomarker candidates, of which 13 had commercial ELISA or Luminex tests available. 16 proteins with ELISA or Luminex tests available were identified by literature review. Further evaluation via Luminex and ELISA and the second round of feature selection using FS-PLS revealed a six-protein signature: three of the included proteins are elevated in bacterial infections (SELE, NGAL, and IFN-γ), and three are elevated in viral infections (IL18, NCAM1, and LG3BP). Performance testing of the signature using Luminex assays revealed area under the receiver operating characteristic curve values between 89·4% and 93·6%. This study has led to the identification of a protein signature that could be ultimately developed into a blood-based point-of-care diagnostic test for rapidly diagnosing bacterial and viral infections in febrile children. Such a test has the potential to greatly improve care of children who are febrile, ensuring that the correct individuals receive antibiotics. European Union's Horizon 2020 research and innovation programme, the European Union's Seventh Framework Programme (EUCLIDS), Imperial Biomedical Research Centre of the National Institute for Health Research, the Wellcome Trust and Medical Research Foundation, Instituto de Salud Carlos III, Consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Grupos de Refeencia Competitiva, Swiss State Secretariat for Education, Research and Innovation.

Clinical relevance of blood urea nitrogen to serum albumin ratio for predicting bacteremia in very young children with febrile urinary tract infection.

Urinary tract infections (UTIs) are one of the most common bacterial infections in febrile children and a common cause of hospitalization, especially in very young children. We examined the clinical characteristics and predictive factors of concomitant bacteremia in pediatric patients with febrile UTI aged ≤24 months. This retrospective multicenter study reviewed medical data from 2,141 patients from three centers from January 2000 to December 2019. Enrolled cases were classified into the bacteremic UTI and non-bacteremic UTI groups according to the presence of blood culture pathogens. Among 2,141 patients with febrile UTI, 40 (1.9%) had concomitant bacteremia. All patients in the bacterial group were aged ≤6 months. Multivariate analysis revealed that younger age, lower blood lymphocyte counts and serum albumin levels, higher C-reactive protein (CRP) levels, blood urea nitrogen (BUN) levels, and BUN/serum albumin ratio were independent risk factors of concomitant bacteremia. The area under the receiver-operating characteristic curves predicting bacteremia were 0.668 for CRP, 0.673 for lymphocytes, and 0.759 for the BUN/albumin ratio. The present study identified the BUN/albumin ratio and lower blood lymphocyte counts as novel predictive factors for bacteremia in young infants with febrile UTI in addition to the previously identified factors of younger age and higher CRP levels. Our findings could help to identify patients at high risk of bacteremia and benefit decision-making in the management of infants with febrile UTI.

A Novel Combination of Host Protein Biomarkers to Distinguish Bacterial From Viral Infections in Febrile Children in Emergency Care.

Distinguishing bacterial and viral infections based on clinical symptoms in febrile children attending the emergency department (ED) is challenging. The aim of this study is to determine a novel combination of host protein biomarkers and to assess its performance in distinguishing between bacterial and viral infection in febrile children attending EDs. A literature search was performed to identify blood protein biomarkers able to distinguish bacterial and viral infections (May 2015-May 2019). We selected 7 protein biomarkers: Procalcitonin, TNF-related apoptosis-inducing ligand (TRAIL), interleukin (IL)-4, IL-6, Interferon gamma-induced protein-10 (CXCL-10), interferon-gamma and lipocalin 2 (LCN2). These were measured in blood plasma using a bead-based immunoassay in children with a confirmed bacterial or viral infection attending EDs in the Netherlands. We used generalized linear modeling to classify bacterial and viral infections and applied a previously developed feature selection algorithm to select the optimal combination of proteins. We performed a subgroup analysis of this protein signature in patients with C-reactive protein <60 mg/L, representing a clinically challenging diagnostic group. In total 102 children were included (N = 67 bacterial; N = 35 viral). Individual performance of the 7 biomarkers in classifying bacterial versus viral infections ranged from 60.8%-74.5% area under the receiver operator curve (AUC). TRAIL, LCN2 and IL-6 were identified as the best 3-protein signature with an AUC of 86% (95% CI: 71.3%-100%). In 57 patients with C-reactive protein levels <60 mg/L, the 3-protein signature had an AUC of 85.1% (95% CI: 75.3%-94.9%). We demonstrate a promising novel combination of 3 host protein biomarkers; TRAIL, LCN2 and IL-6, which performs well in classifying bacterial and viral infections in febrile children in emergency care.

Heart rate and respiratory rate in predicting risk of serious bacterial infection in febrile children given antipyretics: prospective observational study

Clinical algorithms used in the assessment of febrile children in the Paediatric Emergency Departments are commonly based on threshold values for vital signs, which in children with fever are often outside the normal range. Our aim was to assess the diagnostic value of heart and respiratory rate for serious bacterial infection (SBI) in children after temperature lowering following administration of antipyretics. A prospective cohort of children presenting with fever between June 2014 and March 2015 at the Paediatric Emergency Department of a large teaching hospital in London, UK, was performed. Seven hundred forty children aged 1 month–16 years presenting with a fever and ≥ 1 warning signs of SBI given antipyretics were included. Tachycardia or tachypnoea were defined by different threshold values: (a) APLS threshold values, (b) age-specific and temperature-adjusted centiles charts and (c) relative difference in z-score. SBI was defined by a composite reference standard (cultures from a sterile site, microbiology and virology results, radiological abnormalities, expert panel). Persistent tachypnoea after body temperature lowering was an important predictor of SBI (OR 1.92, 95% CI 1.15, 3.30). This effect was only observed for pneumonia but not other SBIs. Threshold values for tachypnoea > 97th centile at repeat measurement achieved high specificity (0.95 (0.93, 0.96)) and positive likelihood ratios (LR + 3.25 (1.73, 6.11)) and may be useful for ruling in SBI, specifically pneumonia. Persistent tachycardia was not an independent predictor of SBI and had limited value as a diagnostic test. Conclusion: Among children given antipyretics, tachypnoea at repeat measurement had some value in predicting SBI and was useful to rule in pneumonia. The diagnostic value of tachycardia was poor. Overreliance on heart rate as a diagnostic feature following body temperature lowering may not be justified to facilitate safe discharge.What is Known:• Abnormal vital signs at triage have limited value as a diagnostic test to identify children with SBI, and fever alters the specificity of commonly used threshold values for vital signs.• The observed temperature response after antipyretics is not a clinically useful indicator to differentiate the cause of febrile illness.What is New:• Persistent tachycardia following reduction in body temperature was not associated with an increased risk of SBI and of poor value as a diagnostic test, whilst persistent tachypnoea may indicate the presence of pneumonia.

Evaluation of CRP as a marker for bacterial infection and malaria in febrile children at the Douala Gyneco-Obstetric and Pediatric Hospital.

C reactive protein (CRP), a marker for the presence of inflammation, has been extensively studied for distinguishing bacterial from non-bacterial infection in febrile patients, but its role in excluding malaria in the febrile child has not been thoroughly evaluated. This was a cross-sectional study at the Douala Gyneco-Obstetric and Pediatric Hospital which included all patients between the ages of one month and 16 years presenting with fever. Consenting patients received complete clinical examinations, then venous blood samples were collected and tested for CRP values, bacterial infection and malaria. Samples of 220 children were analyzed. 142/220 had viral infections, 50/220 had malaria and 49/220 had bacterial infections. 7/220 had both malaria and bacterial infection. There was no significant difference between mean CRP values in malaria and bacterial infection (p = 1), but CRP means were significantly higher in malaria/bacterial infection than in viral infection (p<0.0001). Area Under the Receiver Operating Characteristics Curve (AUROC) values were 0.94 for malaria and 0.86 for bacterial infection, with a calculated cut-off of 23.6mg/L for malaria and 36.2mg/L for bacterial infection. At these cut-offs, CRP had a Positive Predictive Value (PPV) of 68.75% and 85.00% for malaria and bacterial infection respectively, with a Negative Predictive Value (NPV) of 94.74% and 89.05% respectively. CRP can effectively exclude malaria and bacterial infection in febrile children in low-resource settings without the need for additional tests.

529. BV Score (Based on TRAIL, IP-10 and CRP) Accurately Distinguishes Between Bacterial and Viral Infection in Febrile Children: A Multi-Cohort Analysis

Abstract Background BV is a score for differentiating between bacterial and viral etiologies. Recently FDA cleared, it is based on computational integration of the blood levels of three host-proteins (TRAIL, IP-10, CRP). Here we report a multi-cohort analysis validating its diagnostic performance in comparison to a microbiology confirmed reference standard for children recruited in the Netherlands, Germany, Italy, Israel and the United States. Methods Febrile pediatric patients (age &amp;lt; 18) were recruited in Emergency Departments and Urgent Care Centers in the Apollo (NCT04690569), Autopilot (NCT03052088) and Opportunity (NCT01931254) studies. Eligibility criteria included suspicion of acute bacterial or viral infection symptoms for &amp;lt; 7 days in patient deemed to be immunocompetent. BV is indicative of bacterial or viral infection (MeMed BV®) based on pre-defined thresholds: 0 ≤ score &amp;lt; 35 indicates viral (or other non-bacterial) infection, 35 ≤ score ≤ 65 indicates equivocal and 65 &amp;lt; score ≤ 100 indicates bacterial infection (or co-infection). BV performance was assessed against the reference standard. Three experts independently reviewed comprehensive patient data including follow-up data but were blinded to BV. A bacterial or viral microbiology confirmed reference standard required all 3 experts to assign the same etiology in addition to a positive microbiology result supporting the experts’ decision (Figure legend). Results Among the 1,747 children recruited in the 3 studies, 861 were assigned a microbiology confirmed reference standard, with 811 viral and 50 bacterial cases (bacterial prevalence 6%). The median age was 1.8 years (interquartile range: 0.9-3.5 years), 42.3% were female, and 72.7% were diagnosed with respiratory tract infection or unspecified viral infection. BV yielded sensitivity and specificity of 95.6% (95% confidence interval: 84.9%-99.5%) and 95.4% (95%CI: 93.6%-96.8%), and negative predictive value of 99.7% (95%CI: 98.9%-99.9%), with 9.6% of cases yielding equivocal scores. Conclusion BV accurately distinguishes bacterial from viral etiology in microbiology confirmed cases and has the potential to support clinical diagnosis in children presenting to acute care settings. Disclosures Sheldon L. Kaplan, MD, MeMed: Advisor/Consultant|MeMed: Grant/Research Support|Pfizer: Grant/Research Support|Pfizer: Honoraria Cesar A. Arias, MD, PhD, Entasis Phramceuticals: Grant/Research Support|MeMed Diagnostics: Grant/Research Support|Merck: Grant/Research Support Richard G. Bachur, M.D., Appendicitis Biomarker: U.S. Patent|MeMed: Advisor/Consultant|MeMed: Grant/Research Support|UpToDate.com: Honoraria|Wolters-Kluwer: Honoraria Louis J Bont, M.D., MeMed: Principal Investigator (Payment made to institution for conduct of the Opportunity study) Adi Klein, M.D., MeMed: Principal Investigator (Payment made to institution for conduct of the Apollo study) Cihan Papan, M.D., MeMed: Grant/Research Support.

Pilot genome-wide association study of antibody response to inactivated SARS-CoV-2 vaccines

Vaccines are a key weapon against the COVID-19 pandemic caused by SARS-CoV-2. However, there are inter-individual differences in immune response to SARS-CoV-2 vaccines and genetic contributions to these differences have barely been investigated. Here, we performed genome-wide association study (GWAS) of antibody levels in 168 inactivated SARS-CoV-2 vaccine recipients. A total of 177 SNPs, corresponding to 41 independent loci, were identified to be associated with IgG, total antibodies or neutral antibodies. Specifically, the rs4543780, the intronic variant of FAM89A gene, was associated with total antibodies level and was annotated as a potential regulatory variant affecting gene expression of FAM89A, a biomarker differentiating bacterial from viral infections in febrile children. These findings might advance our knowledge of the molecular mechanisms driving immunity to SARS-CoV-2 vaccine.

Frequency of Urinary Tract Infection in Febrile Children without Any Focus on Infection

Background: In newborns and young children, a urinary tract infection is a frequent hidden cause of fever. Children younger than a year old who appear with fever and symptoms of UTI are usually given treatment for something else. Objectives: The objective of this study was to assess the prevalence of UTI in children presenting to a tertiary care hospital between the ages of 1 month and 36 months with nonspecific fever. Duration and study settings: The Children's Hospital Pakistan Institute of Medical Science, SZABMU, Islamabad, was the site of this trial, which ran from Jan 2018 to June 2018. Study design: Descriptive cross sectional Methodology: After a complete medical history and physical examination, a urine sample was taken for testing and culture using a soft tube in younger children and a clean catch approach in older children or those who are cooperative. Urisys 2400 was used to analyse the urine samples. Larger children's urine samples were grown on CLED agar plates (cysteine lactose, electrolyte deficient). Clinitek Siemens, a haematology analyser, was used to determine the number of white blood cells in the blood. The Pakistan Institute of Medical Sciences in Islamabad is home to a state-of-the-art laboratory where tests including leucocyte count, urine DR, and culture were conducted. A pre-designed proforma was used to record the patient's demographic information, medical history, diagnosis, and laboratory results. Results: In this study, 6.47 percent (n=18) of 278 children aged 1 to 36 who presented to a tertiary care hospital with a fever and no other obvious signs of infection were found to have a urinary tract infection. Conclusion: Children arriving to a tertiary care hospital with a fever and no other signs of infection are not likely to have a urinary tract infection. Keywords: UTI in children with diffuse fever and no obvious source of infection.

Frequency of culture positive urinary tract infection in febrile children.

Objective: To determine prevalence, causative organisms and sensitivity patterns of urinary1tract infections in febrile children. Study Design: Cross Sectional study. Setting: National Institute of Child Health, Karachi. Period: Jan 2019 to July 2019. Material &amp; Methods: Patients from 3.0 to 14.0 years of age of either sex with complain of fever of &gt;37.5 C for less than 2.0 weeks were included. Patients who have life threatening conditions, chronically ill, received antibiotics within 48 hours or had structural abnormalities of urinary tract like posterior ureteral valves and children with renal failure were excluded from study. Urinary sample was collected following aseptic measures of febrile children ad was sent to lab for culture and sensitivity within one hour of its collection. Sensitivity pattern was measured in lab via disc diffusion method. Data was analyzed using SPSS version 22. Results: The mean age was 8.6±3.3 years out of which 115 (65.7%) were male and 60 (34.3%) were females, mean duration of illness was 8.7±3.1 days. The frequency of culture positive UTI in febrile children was 21 (12%) cases. The common pathogen isolated from the urine culture was E. coli found in 10 cases followed by Klebsiella oxytoca. Overall 70% of E. coli are sensitive to. gentamicin and amikacin, 50% were sensitive to third generation cephalosporin, 60% of Klebsiella are sensitive to third generation cephalosporin, 60% resistant to gentamicin and amikacin and 80% were resistant to ampicillin. Conclusion: It was concluded from this study that the frequency of culture positive urinary tract infections in febrile children was 12% and common pathogen was E.coli followed by klebsilla oxytoca.

Malaria rapid diagnostic tests for the case management of febrile children in Nigerian primary healthcare settings: a cross-sectional study

BackgroundMalaria has been identified as a significant public health burden, exhibiting a high risk of death and morbidity. In sub-Saharan Africa, most young children attending primary healthcare facilities are commonly diagnosed with malaria. Thus, introduction of malaria rapid diagnostic test (mRDT) kits and effective antimalarials has substantially improved the management of malaria cases. However, healthcare worker confidence and adherence to procedures dependent on malaria test results remain variable in high-burden settings due to lacking alternative point-of-care tests to diagnose other causes of fever. In this study, we compared the results of malaria screenings using mRDT and microscopy in febrile children presenting at a primary health facility.MethodsThis study was conducted at a primary health center in Owo, Ondo State, Nigeria. Children with fever were assessed for malaria by health staff and, where indicated, screened using Plasmodium falciparum histidine-rich protein-2 mRDT kits. Blood samples were collected on slides for microscopy and in hematocrit tubes for hematocrit determination simultaneously, whereas the mRDT test was done by routine health staff. Children found positive for malaria via mRDT were diagnosed as uncomplicated malaria cases and treated as outpatients using artemether-lumefantrine. Blood slides were read independently by two trained microscopists blinded to the mRDT results. The parasite densities were defined as average counts by both microscopists. We then assessed the sensitivity, specificity, and predictive value of mRDT for the diagnosis of malaria.ResultsWe compared the test results of 250 febrile children who are under 15 years old. The test positivity rates were 93.6% (234/250) and 97.2% (243/250) using microscopy and rapid RDTs, respectively. The sensitivity and specificity of mRDT compared to microscopy were 100.0% and 43.8%, respectively, with a positive predictive value of 96.3% (95% CI 93.1–98.3). The hematocrit value was <30% in 64% of the children.ConclusionAs per our findings, mRDTs have correctly detected infections in febrile children. Healthcare workers and caregivers should be encouraged to act in accordance with the test results by means of regular feedback on the quality of mRDTs in use in malaria case management.

Caregivers’ vector control methods and its effect on malaria infection in febrile children presenting in a Tertiary Hospital in Nigeria

Background: Malaria is a major public health problem in sub-Saharan Africa. Several efforts are being made to reduce its prevalence and morbidity in Nigerian children with emphasison vector control measures.Methods: This was acrosssectional descriptive study conducted on 382 febrile children seen at a tertiary hospital in Nigeria over an eight-month period. A structured questionnaire was used to collect information on sociodemographic, vector control measures and care given to the subjects. Investigations conducted included malaria microscopy and total leukocyte count.Results: Eighty percent (308/382) employed at least one vector controlmeasures to prevent malaria infection, and majority 232 (75.2%) use only one control measure. The commonest control measures used included always keeping doors and windows shut 298 (96.7%) and/or netted 280 (90.9%), use of conventional insecticide sprays 183 (59.4%), use of insecticide treated bed nets (ITNs) 178 (57.8%) and ensuring child sleeps at night with body adequately covered 77(25%). Approximately half (178/315) of households who owned ITN used it, and only 40.4% (72/178) used it daily. It was noted that children that slept under an insecticide treated bed net (RR 0.56, 95% CI 0.33-0.94; P=0.029) and those who slept well covered at night (RR 0.26, 95% CI 0.12-0.61; P=0.002) had less risk of malaria infection. The use insecticide treated bed net however lost significance following adjustment for other control measures used and socio-demographic factors of interest (RR 0.63, 95% CI 0.36-1.10;P=0.101).Conclusion: There is need to intensify education on appropriate malaria control measures especially proper use of insecticide-treated nets and suitable clothing during sleep at night.

Evaluation of CRP as a Marker for Malaria and Bacterial Infection in Febrile Children at Douala Gyneco-Obstetric and Pediatric Hospital

Evaluation of CRP as a Marker for Malaria and Bacterial Infection in Febrile Children at Douala Gyneco-Obstetric and Pediatric Hospital

Prevalence of urinary tract infection in febrile children of less than five years of age

To determine the prevalence of urinary tract infection in febrile children, less than 5 years of age. To assess the validity of microscopic urine analysis and urine culture in the diagnosis of urinary tract infection.Prospective study. Children attending the department of paediatrics, Dr.V.R.K. Women’s Medical College, Teaching Hospital &amp; Research Centre, with febrile illness during June 2019-June 2020.370 children between 1 month to 5 years of age.Data related to age, sex, nutritional status, socioeconomic status and predisposing risk factors like urethral instrumentation, bowel habits etc, were noted. A thorough physical examination with relevant investigations were carried out in all these patients. Routine urinary microscopy was done in all patients and urine culture was done in those who showed pyuria of &amp;#62;5 pus cells/HPF in centrifuged urine sample.In our study, overall prevalence of UTI was 3.5% in children between 1 month to 5 yrs and 4.1% in children &amp;#60;2yrs and 7% in Children &amp;#60;1 year of age with M:F ratio of 1:1in children &amp;#60;2yrs. Prevalence of culture positivity was 44% in those who showed &amp;#62;10 pus cells/HPF in centrifuged sample of urine and 2.5% in those who showed &amp;#62;5pus cells/HPF.The presence of obvious source of fever such as upper respiratory tract infection or otitis media is not reliable in excluding urinary tract infection. Overall prevalence of UTI in our study was low (3.5%) and prevalence among children &amp;#60;2yrs was 4.1% and &amp;#60;1 year of age was 7%. Pyuria of &amp;#62;5pus cells/HPF (centrifuged urine sample) should be considered as significant and further evaluation should be done to initiate prompt treatment.

Transcript host-RNA signatures to discriminate bacterial and viral infections in febrile children.

Traditional laboratory markers, such as white blood cell count, C-reactive protein, and procalcitonin, failed to discriminate viral and bacterial infections in children. The lack of an accurate diagnostic test has a negative impact on child's care, limiting the ability of early diagnosis and appropriate management of children. This, on the one hand, may lead to delayed recognition of sepsis and severe bacterial infections, which still represent the leading causes of child morbidity and mortality. On the other hand, this may lead to overuse of empiric antibiotic therapies, particularly for specific subgroups of patients, such as infants younger than 90 days of life or neutropenic patients. This approach has an adverse effect on costs, antibiotic resistance, and pediatric microbiota. Transcript host-RNA signatures are a new tool used to differentiate viral from bacterial infections by analyzing the transcriptional biosignatures of RNA in host leukocytes. In this systematic review, we evaluate the efficacy and the possible application of this new diagnostic method in febrile children, along with challenges in its implementation. Our review support the growing evidence that the application of these new tools can improve the characterization of the spectrum of bacterial and viral infections and optimize the use of antibiotics in children. IMPACT: Transcript host RNA signatures may allow to better characterize the spectrum of viral, bacterial, and inflammatory illnesses in febrile children and can be used with traditional diagnostic methods to determine if and when to start antibiotic therapy. This is the first review on the use of transcript RNA signatures in febrile children to distinguish viral from bacterial infections. Our review identified a wide variability of target populations and gold standards used to define sepsis and SBIs, limiting the generalization of our findings.

112. A Rapid Host-Protein Signature Based on TNF-related Apoptosis-Induced Ligand (TRAIL), Interferon Gamma Induced Protein-10 (IP-10) and C-Reactive Protein (CRP) Accurately Differentiates Between Bacterial and Viral Infection in Febrile Children: Apollo Sub-Study

BackgroundIdentifying infectious etiology is essential for appropriate patient management, including antibiotic use. A host-protein signature for differentiating bacterial from viral infection has exhibited robust performance (AUC of 0.9, 95% CI 0.86-0.95) in prior studies. Performance data was lacking for a broad pediatric population recruited in emergency departments (EDs) and urgent care centers (UCCs).MethodsNon-immunocompromised children were recruited prospectively from 5 EDs and 3 UCCs in the U.S. and 1 ED in Israel between May 2019 and August 2020. Eligibility required physician’s clinical suspicion of acute infection and reported fever. Reference standard etiology was adjudicated by experts based on clinical, laboratory, radiological, microbiological and follow-up data. For the primary analysis, experts blinded to one another, to the host-signature results and also to procalcitonin and CRP, classified cases as bacterial or viral. For the secondary analysis, experts blinded to one another and the host signature results, were permitted to classify cases as bacterial, viral or indeterminate; indeterminates were removed from the secondary analysis. Host signature (comprising TRAIL, IP-10 and CRP; MeMed BV®) was measured using a rapid platform (MeMed Key®) generating a bacterial likelihood score (0-100) in 15 minutes.ResultsThe study cohort comprised 162 children (median age, 5.5 yrs; interquartile range, 8.5), of whom 69 (43%) presented within 2 days of symptom onset and 37 (23%) were hospitalized for a median of 3 days. Respiratory tract infection was the predominant syndrome (11% lower and 44% upper). Host signature attained AUC 0.87 (0.74-1) and 0.92 (0.79-1) in the primary and secondary analysis, respectively. With higher the signature score, there was a significantly higher likelihood of bacterial infection (p< 0.001; Table 1). The 3 bacterial infections assigned score < 35 (false negative) would have been identifiable by physical examination (Table 2).Increasing host signature score is associated with increasing likelihood of bacterial infection across both the primary and secondary cohort The performance of the host signature score in differentiating between bacterial and viral infection was evaluated by allocating children to one of five score bins and within each bin according to their adjudication label and determining if there is a meaningful increase in the relative likelihood of bacterial infection across the bins based on the Cochrane-Armitage test of trend. PPV, positive predictive value. NPV, negative predictive value. *Includes patients adjudicated as non-infectiousThree children assigned a bacterial adjudication label and a score of 35 or less (false negatives) have bacterial infections identifiable in physical exam ConclusionThe host-protein signature measured using a rapid platform attained robust performance in differentiating bacterial vs viral infection in children with acute febrile illness, supporting its potential to enhance rational use of antibiotics in the ED and UCC. Disclosures Sheldon L. Kaplan, MD, Pfizer (Research Grant or Support) Mark Kellogg, PhD, MeMed (Scientific Research Study Investigator) Andrea T. Cruz, MD, MPH, American Academy of Pediatrics (Individual(s) Involved: Self): editorial board member Kristina G. Hulten, PhD, Pfizer (Research Grant or Support) Cesar A. Arias, M.D., MSc, Ph.D., FIDSA, Entasis Therapeutics (Grant/Research Support)MeMed Diagnostics (Grant/Research Support)Merk (Grant/Research Support) Richard Gordon, MD, MeMed (Scientific Research Study Investigator) Sergey Motov, MD, MeMed (Scientific Research Study Investigator) Theresa Jacob, PHD MPH, MeMed (Scientific Research Study Investigator) Natasha Ballard, MD, MeMed (Scientific Research Study Investigator) George Suits, MD, MeMed (Scientific Research Study Investigator) Jeffrey Harris, MD, MeMed (Scientific Research Study Investigator) Maanit Shapira, Ph.D, MeMed (Scientific Research Study Investigator) Richard E. Rothman, PhD, MD, Chem bio (Grant/Research Support) Karen C. Carroll, MD, MeMed (Scientific Research Study Investigator)Meridian Diagnostics, Inc. (Grant/Research Support)Pattern Diagnostics (Advisor or Review Panel member)Scanogen, Inc. (Advisor or Review Panel member) Karen C. Carroll, MD, Pattern Diagnostics, Inc. (Individual(s) Involved: Self): Grant/Research Support; Scanogen, Inc. (Individual(s) Involved: Self): Consultant Leticia M. Ryan, MD MPH, MeMed (Scientific Research Study Investigator) Richard Bachur, MD, MeMed (Scientific Research Study Investigator)