Pathogens In Children Research Articles

Evaluation of renal effects of liposomal amphotericin B in children with malignancies with KDIGO and RIFLE criteria

BackgroundAmphotericin B is a broad-spectrum antifungal agent and is the backbone of the treatment for medically important opportunistic fungal pathogens in children. This study aimed to compare the nephrotoxicity associated with L-AmB in children with acute lymphoblastic leukemia and acute myeloid leukemia. Materials and methodsA total of 112 pediatric acute lymphoblastic leukemia or acute myeloid leukemia patients who received treatment with L-AmB (Ambisome®) at the University of Health Sciences Dr Behcet Uz Children's Hospital over 7 years were included. The incidence of hypokalemia, decreased estimated glomerular filtration rate and presence of acute kidney injury was recorded. ResultsThe average L-AmB treatment duration was 17.1±15.0 days. Five patients (4.4%) of the patients had grade I acute renal injury according to KDIGO criteria and 16 patients (14.2%) had increased risk for kidney injury according to RIFLE criteria. There were no patients with eGFR decrease above 50% and no renal injury and failure were observed during L-AmB treatment. The rate of patients with hypokalemia in the pre-treatment was 17.9% and the post-L-AmB group was 50.0%. The rate of hypokalemia was higher in the post-treatment group (P=0.0015). Among the 112 patients, only two patients (1.7%) required cessation of L-AmB treatment due to resistant hypokalemia despite supplementation. ConclusionsHypokalemia was more common compared to glomerulotoxicity and acute renal injury (according to KDIGO and RIFLE criteria) in pediatric leukemia patients treated with L-AmB. Hypokalemia developed in nearly half of the patients and the study shows the need for randomized controlled trials and strategies for hypokalemia associated with L-AmB treatment.

Genomic Diversity and Antimicrobial Resistance of Haemophilus Colonizing the Airways of Young Children with Cystic Fibrosis.

Respiratory infection during childhood is a key risk factor in early cystic fibrosis (CF) lung disease progression. Haemophilus influenzae and Haemophilus parainfluenzae are routinely isolated from the lungs of children with CF; however, little is known about the frequency and characteristics of Haemophilus colonization in this context. Here, we describe the detection, antimicrobial resistance (AMR), and genome sequencing of H. influenzae and H. parainfluenzae isolated from airway samples of 147 participants aged ≤12 years enrolled in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) program, Melbourne, Australia. The frequency of colonization per visit was 4.6% for H. influenzae and 32.1% for H. parainfluenzae, 80.3% of participants had H. influenzae and/or H. parainfluenzae detected on at least one visit, and using genomic data, we estimate 15.6% of participants had persistent colonization with the same strain for at least two consecutive visits. Isolates were genetically diverse and AMR was common, with 52% of H. influenzae and 82% of H. parainfluenzae displaying resistance to at least one drug. The genetic basis for AMR could be identified in most cases; putative novel determinants include a new plasmid encoding blaTEM-1 (ampicillin resistance), a new inhibitor-resistant blaTEM allele (augmentin resistance), and previously unreported mutations in chromosomally carried genes (pbp3, ampicillin resistance; folA/folP, cotrimoxazole resistance; rpoB, rifampicin resistance). Acquired AMR genes were more common in H. parainfluenzae than H. influenzae (51% versus 21%, P = 0.0107) and were mostly associated with the ICEHin mobile element carrying blaTEM-1, resulting in more ampicillin resistance in H. parainfluenzae (73% versus 30%, P = 0.0004). Genomic data identified six potential instances of Haemophilus transmission between participants, of which three involved participants who shared clinic visit days. IMPORTANCE Cystic fibrosis (CF) lung disease begins during infancy, and acute respiratory infections increase the risk of early disease development and progression. Microbes involved in advanced stages of CF are well characterized, but less is known about early respiratory colonizers. We report the population dynamics and genomic determinants of AMR in two early colonizer species, namely, Haemophilus influenzae and Haemophilus parainfluenzae, collected from a pediatric CF cohort. This investigation also reveals that H. parainfluenzae has a high frequency of AMR carried on mobile elements that may act as a potential reservoir for the emergence and spread of AMR to H. influenzae, which has greater clinical significance as a respiratory pathogen in children. This study provides insight into the evolution of AMR and the colonization of H. influenzae and H. parainfluenzae in a pediatric CF cohort, which will help inform future treatment.

Etiologies of Hospitalized Acute Bronchiolitis in Children 2 Years of Age and Younger: A 3 Years' Study During a Pertussis Epidemic.

Objective: In recent years, the incidence of Bordetella pertussis infection in infants and young children has been increasing. Multiple studies have suggested that B. pertussis may be one of the pathogens of bronchiolitis in infants and young children. However, the prevalence and clinic characteristic of B. pertussis in bronchiolitis is controversial. This prospective descriptive study evaluated the prevalence and clinical manifestations of infants and young children hospitalized for bronchiolitis with B. pertussis.Methods: Children hospitalized with bronchiolitis were eligible for a prospective study for 36 months from January 1, 2017, to December 31, 2019. Besides B. pertussis, 10 common respiratory viruses and Mycoplasma pneumoniae (MP) were confirmed by laboratory tests. Medical records of patients were reviewed for demographic, clinical characteristics, and laboratory examination.Results: A total of 1,092 patients with bronchiolitis were admitted. B. pertussis was detected in 78/1,092 (7.1%) patients. Of the 78 patients with B. pertussis bronchiolitis, coinfections occurred in 45 (57.7%) patients, most frequently with human rhinovirus (28/78, 35.9%), followed by MP (9/78, 11.4%), and human bocavirus (6/78, 7.7%). The peak incidence of B. pertussis infection was in May. A high leukocyte count could help distinguish B. pertussis–associated acute bronchiolitis from other acute bronchiolitis etiologies. After excluding coinfections, children with B. pertussis–only bronchiolitis exhibited a milder clinical presentation than those with RSV-only infection; also, children with MP-only and other pathogen infections revealed similar severity. The morbidity of B. pertussis was common (31/78, 39.7%) in infants with bronchiolitis under 3 months.Conclusion: In summary, B. pertussis is one of the pathogens in children with bronchiolitis, and coinfection of B. pertussis with other viruses is common in bronchiolitis. B. pertussis should be considered when patients hospitalized with bronchiolitis present a longer course and have an elevated leukocyte count. Patients with B. pertussis–associated bronchiolitis present a milder clinical presentation.

#31: Children with Invasive S. aureus Infection Produce Broadly Neutralizing Antibodies Against Distantly Related Variants of the Cytotoxin LukAB

Abstract Background Staphylococcus aureus is the most common invasive bacterial pathogen in children, and novel targets of intervention are urgently needed. The two-component leukotoxin, LukAB, is critical for S. aureus targeting and killing of human neutrophils and is abundantly produced in the setting of invasive human infection. LukAB is unique among S. aureus cytotoxins in that it exists in variant form across distantly related strains of clinically relevant S. aureus. The broad diversity of circulating clinical S. aureus strains must be taken into account to successfully develop new anti-staphylococcal preventives or therapeutics. This diversity and ongoing S. aureus evolution may explain previous unsuccessful attempts to intervene against S. aureus at the virulence factor level. We have previously shown that LukAB is ubiquitous among clinical isolates and that children with invasive disease mount a high-titer neutralizing response, but the breadth of function of this response has not previously been explored. Methods B-cells were isolated from children with invasive S. aureus infections (e.g. bacteremia or acute hematogenous osteomyelitis). Following EBV-transformation, cell supernatants were screened for LukAB binding and selected for generation of monoclonal hybridomas. MAbs were assessed for binding by ELISA and neutralizing function by in vitro cytotoxicity assays, where neutrophil-like HL-60 cells were cultured in the presence of human mAbs and diverse allelic variants of LukAB. The infecting S. aureus isolates were typed using multilocus sequence typing (MLST) to determine clonal complexes. Results 34 distinct human anti-LukAB mAbs were generated from 3 children with invasive S. aureus disease. Of these, 22% were isolated following infection with a strain belonging to clonal complex 8 (CC8), consistent with the epidemic USA300 clone, and 78% were generated against CC5 strains. Within this panel, all mAbs potently neutralized LukAB from the same clonal complex as the corresponding infecting isolate, but 23 also demonstrated neutralization against other allelic variants of LukAB. 7 mAbs were capable of broad, potent neutralization against LukAB variants from all clinically relevant clonal complexes tested (CC8, CC30, CC45, CC75, CC1, CC5, and CC398). Conclusions A subset of human mAbs isolated from children with invasive S. aureus disease were capable of broad neutralization against distantly related variants of the important toxin LukAB. This has two important implications: First, we found strong evidence of a conserved target (or targets) for antibody-mediated toxin neutralization across diverse strains of S. aureus. Second, this provides additional support for this toxin as a target of intervention, as some previous vaccine attempts were likely unsuccessful due to activity against a narrow subset of circulating S. aureus strains.

Epidemiology of Respiratory Pathogens Among Children Hospitalized for Pneumonia in Xiamen: A Retrospective Study.

ObjectivesTo investigate the etiology of common respiratory pathogens in children < 2 years of age hospitalized with pneumonia in Xiamen from 2014 to 2017.MethodsThe medical records of 5581 children with pneumonia were retrospectively reviewed. Direct immunofluorescent test was used for respiratory virus testing. Bacteria were detected by conventional culture method. The results of pathogen detection at admission were analyzed as well as the clinical outcomes of children.ResultsThe burden of hospitalized children with pneumonia was highest among infants < 6 months old (58.2%). Respiratory syncytial virus (RSV) was the most common respiratory virus (26.0%) followed by parainfluenza (4.8%) and adenovirus (3.2%). Haemophilus influenzae was the most common bacteria detected (16.6%) followed by Moraxella catarrhalis (13.4%), Staphylococcus aureus (13.0%), Streptococcus pneumoniae (12.3%), Escherichia coli (5.1%) and Klebsiella pneumoniae (4.8%). Notably, RSV and K. pneumoniae were detected more frequently in severe pneumonia (35.0% and 10.9%) versus mild pneumonia (25.6% and 4.6%), with higher rates of ICU admissions, longer hospital stays and higher hospital costs compared to those infected with other respiratory pathogens.ConclusionsAmong children < 2 years of age hospitalized with pneumonia in Xiamen, RSV was the most common respiratory virus, while H. influenzae and S. pneumoniae remained the predominant bacterial pathogens detected. Considering the low implementation rate of vaccines against pneumococcal and Hib pneumonia in China, there is an urgent need to increase both vaccination rates to reduce pneumococcal and Hib disease burden.

The role of Staphylococcus lugdunensis as a pathogen in children: a multicentre retrospective study.

Introduction: Staphylococcus lugdunensis (SL), a tube coagulase negative Staphylococcus, is known to be pathogenic in adults, causing mainly skin infections.Gap Statement: Previous studies assessing SL's role in paediatric populations are sparse and are mainly limited to case reports.Aim: Present the clinical characteristics consistent with SL infections and its putative role as a pathogen in the paediatric population.Methodology: A retrospective multicentre study was conducted in four paediatric medical centres in Israel. Patients with isolates of SL presenting between 2009-2019 were included.Results: SL was isolated from 40 patients. Average (±SD) age at presentation was 5.9 (±6.2) years, with 22 (55 %) being female. Skin, soft tissue and musculoskeletal infections were the most common (n=20, 50%) followed by ear infections (n=13, 32.5%). Five cases of urine isolates and two isolates from blood culture samples were also reported. Skin abscess was the most common infection among skin and soft tissue isolates, reported in 17 children (85%) with SL being the only pathogen in 15 (75%). Otitis media was the most common ear infection accounting for 12 (92%) of all cases with SL as the only isolate reported in 6 (46%). Five cases of SL isolates from urine specimens were reported, all of which with poor growth of bacteria and normal urinalysis. Two cases of SL growth in blood culture were found in children presenting with signs and symptoms consistent with invasive blood stream infection.Conclusions: In the paediatric population, studied infections caused by SL are increasingly observed. The results of this study highlight its role as a pathogen in soft tissue infections and its putative role in otitis media and invasive blood stream infections. However, the role of SL as an uropathogen was not established.

Antibiotic resistance patterns of urinary tract pathogens in children from Central Romania.

One of the most frequent bacterial infections in children are urinary tract infections (UTIs). In recent years, an increasing incidence of UTIs caused by resistant bacterial strains has been observed, especially with extended-spectrum β-lactamase-producing Enterobacteriaceae that represent about 15% of UTIs. A retrospective study was performed comprising 331 pediatric cases with UTI. Our study aimed to detect the resistance of the uropathogens to common drugs used in UTI treatment. High resistance rates have been recorded for ampicillin, amoxicillin, trimethoprim/sulfamethoxazole (TMP/SMX), cefuroxime, and ciprofloxacin, among E. coli and Klebsiella. The multidrug-resistance (MDR) rate was detected in one-third of the uropathogens, among which more than half were isolated in patients with urinary tract abnormalities. Our study highlighted that nitrofurantoin, ceftriaxone, amikacin and carbapenem may be used for the empirical treatment for febrile or complicated UTI in children. This is the first comprehensive study that evaluates antibiotic resistance in UTIs in children, and their association with urinary tract abnormalities in Romania. As a result of this research, the protocol for initial empiric treatment of infants with febrile or complicated UTI should be modified considering a detailed and ongoing monitoring of local sensitivity of uropathogens to antimicrobial agents.

Pediatric Enteric Diagnostic Stewardship: The Right Test in the Right Context.

In this issue of Pediatrics , Cotter et al1 offer valuable analysis of the utility of molecular (nucleic acid amplification) enteric pathogen diagnostic technology in hospitalized children. These tests return highly worthwhile information for some infections, but many of their results are prone to misinterpretation. However, diagnostic guidelines based on classic microbiologic techniques do not perform well either.2 Molecular enteric microbiology is, therefore, a model opportunity for diagnostic stewardship to maximize worth and minimize wasteful expense. Cotter et al1 find that only 3.7% of tested hospitalized children benefitted from molecular diagnosis in terms of decreased length of stay and/or initiation of appropriate treatment. These data reinforce previous findings: enteric diagnostic use increases briskly after molecular testing becomes available and the tests find many unexpected signals reflecting difficult-to-interpret and/or nonactionable microbes. The authors candidly acknowledge the study’s limitations: nongeneralizability (their findings do not apply to outpatients) and reliance on historic comparison data. The benefit they cite applies to hospitalized children, and such populations are probably enriched for severe bacterial infections for which rapid and accurate molecular diagnosis has the greatest value; one would expect different yields in emergency facilities and ambulatory settings. … Address correspondence to Gillian A. M. Tarr, PhD, School of Public Health, University of Minnesota, MMC 807, 420 Delaware St SE, Minneapolis, MN 55455. E-mail: gtarr{at}umn.edu

Detection and Analysis of Respiratory Pathogens in Hospitalized Children with Acute Respiratory Tract Infections by a Multiplex-PCR Assay Based on the Genetic Analyzer Platform

Background: Despite the considerable incidence of acute respiratory tract infections (ARTI) among children in Henan province, detailed epidemiological information is limited. Objectives: Following a retrospective design, the current study aimed to analyze the epidemiological trends of respiratory pathogens in children hospitalized at Henan Children’s Hospital. Methods: A total of 11306 children (age range, 4 days to 15 years) diagnosed with ARTI admitted to Henan Children’s Hospital from March 1, 2019, to February 29, 2020, were enrolled. Nasopharyngeal swabs, alveolar lavage fluid, or sputum samples were analyzed for the presence of 12 pathogens via a multiplex-PCR assay based on the Genetic Analyzer platform. Data of 11306 samples were eligible for analysis. Results: The total positive rate was 78.1% (8831/11306). Of 8831 positive samples, 7017 (79.5%, 7017/8831) had a single pathogen and 1814 (20.5%, 1814/11306) had multiple pathogens. Human rhinovirus was the most common pathogen (25.4%, 2874/11306), followed by mycoplasma (18.1%, 2050/11306) and human respiratory syncytial virus (15.8%, 1783/11306). There was no significant difference concerning the positive rate of respiratory pathogens between boys and girls (χ2 = 0.286, P = 0.593). Children were more likely to be infected in autumn and winter than in spring and summer (9722 vs. 1584, respectively). Conclusions: Human rhinovirus and mycoplasma were the most commonly detected pathogens. The positive rate of chlamydia was independent of the season, while positive rates of other pathogens were season-related. The positive rate of influenza A (H1N1) was independent of age, while for other pathogens, it was age-dependent. This study demonstrated species-level information on the pathogens, which can improve the prevention and treatment of hospitalized children with ARTI.

Prevalence and Antibiotic Susceptibility of Bacterial Pathogens in Children with Acute Otitis Media - A Retrospective Study at Tertiary care Teaching Hospital, India

Prevalence and Antibiotic Susceptibility of Bacterial Pathogens in Children with Acute Otitis Media - A Retrospective Study at Tertiary care Teaching Hospital, India

Children with Primary Septic Arthritis Have a Markedly Lower Risk of Adverse Outcomes Than Those with Contiguous Osteomyelitis.

It is widely believed that septic arthritis poses a risk of joint destruction and long-term adverse outcomes for children if not treated emergently. In the present study, children who had primary confirmed septic arthritis were compared with those who had septic arthritis and adjacent osteomyelitis to evaluate differences that affect the relative risk of adverse outcomes. Children who underwent multidisciplinary treatment for septic arthritis with or without contiguous osteomyelitis between 2009 and 2019 were retrospectively studied. Clinical, laboratory, treatment, and outcome data were compared between cohorts of children with primary confirmed septic arthritis and children with septic arthritis and contiguous osteomyelitis. One hundred and thirty-four children had primary confirmed septic arthritis, and 105 children had septic arthritis with contiguous osteomyelitis. Children with osteomyelitis were older (median, 7.4 versus 2.4 years), had higher initial C-reactive protein (median, 15.7 versus 6.4 mg/dL), and had a higher rate of thrombocytopenia (21.0% versus 1.5%). They also had a higher rate of bacteremia (69.5% versus 20.2%) for a longer duration (median, 2.0 versus 1.0 days). Detected pathogens in children with osteomyelitis as compared with those with primary septic arthritis were more likely to be Staphylococcus aureus (77.1% versus 32.1%) and less likely to be Kingella kingae (2.9% versus 32.1%). Children with contiguous osteomyelitis had longer hospitalizations (median, 8.0 versus 4.0 days), a higher rate of intensive care (21.0% versus 1.5%), a higher readmission rate (17.1% versus 5.2%), and a higher complication rate (38.1% versus 0.7%). Primary septic arthritis in children is dissimilar to septic arthritis associated with osteomyelitis. The present study demonstrates that long-term adverse outcomes in children with septic arthritis are likely due to the contiguous osteomyelitis. Children with primary septic arthritis are sufficiently distinguishable from those who have contiguous osteomyelitis to guide decisions for magnetic resonance imaging acquisition, duration of antibiotic therapy, and length of outpatient follow-up in order to recognize and address adverse outcomes. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Species composition of community–acquired pneumonia pathogens in children in assosiation with decreed pneumococcal conjugated vaccine immunisations

Based on the results of selective molecular genetic studies, the species structure of the community-acquired pneumonia pathogens in children of Perm was studied in association with the decreed vaccination against pneumococcal infection in 2014–2019. It has been established that in recent years, against a background of an increase in the volume of decreed immunisations with the conjugated pneumococcal vaccine Prevenar 13, there is a decrease in the frequency of extraction in patients with Streptococcus pneumoniae and, on the contrary, an increase in the frequency of Mycoplasma pneumoniae extraction.

Clinical, biological and bacteriological characteristics of osteoarticular infections in infants less than 12 months of age.

Aim: This retrospective study's objective was to evaluate osteoarticular infectionin infants less than 12 months of age, with a particular focus on biological features and bacteriological etiology. Material & methods: We retrospectively reviewed the medical records of every infant younger than 12 months old admitted in our institution for a suspected osteoarticular infection between January 1980 and December 2016. Results: Sixty-nine patients records were reviewed, including eight neonates, 16 infants from 1 to5 months old, and 45 from 6 to12 months old. Conclusion: Neonates and infants aged from 6 to 12 months old were more exposed to infections. Staphylococcus aureus remained the main pathogen in children <6 months, whereas Kingella kingae has become the most frequently isolated microorganism in infants aged from 6 to 12 months old.

Konya yöresindeki akut gastroenteritli çocukların değerlendirilmesi

Introduction: Acute gastroenteritis is a major cause of pediatric morbidity and mortality around the world. It remains a frequent reason for infection-related admissions to emergency units among all age groups. Epidemiologic knowledge about etiology of gastroenteritis in a certain area allows early and correct diagnosis. The current study aimed at evaluating the prevalence of bacterial, viral, and parasitic pathogens in children with gastroenteritis who admitted to pediatric emergency unit. Methods: The demographic, clinical and laboratory data of 450 children with acute gastroenteritis, within the age range of 0 months to 18 years who admitted to Pediatric Emergency Department of Meram Faculty of Medicine from September 2018 to September 2019 were retrospectively analyzed.Results: While 31.10% of the patients had etiological agents, 68.90% of the patients could not be identified. The identified pathogens were 2.10% bacteria, 82.20% virus, 15.70% parasite. The most common pathogen was Rotavirus with a rate of 72.90%. This was followed by E. histolytica with 15.00% and Adenovirus with 9.30%. Rotavirus was most frequently detected at the age of 2 years, and E. histolytica was most frequently detected at the age of 5 years. Rotavirus was most common in the winter season [33.7%]. 7.10% of the patients were hospitalized. The average length of hospital stay was 3.34 ± 2.19 days.Conclusion: Rotavirus, E. histolytica and Adenovirus were the most prevalent agents of diarrhea in children aged 0 month to 18 years who admitted to emergency unit in this study.

Elevated Extracellular cGMP Produced after Exposure to Enterotoxigenic Escherichia coli Heat-Stable Toxin Induces Epithelial IL-33 Release and Alters Intestinal Immunity.

Enterotoxigenic Escherichia coli (ETEC) is a major diarrheal pathogen in children in low- to middle-income countries. Previous studies identified heat-stable enterotoxin (ST)-producing ETEC as a prevalent diarrheal pathogen in children younger than 5 years. While many studies have evaluated the interaction of ETEC heat-labile enterotoxin (LT) with host epithelium and immunity, few investigations have attempted similar studies with ST. To further understand ST pathogenesis, we examined the impact of ST on cGMP localization, epithelial cell cytokine production, and antibody development following immunization. In addition to robust intracellular cGMP in T84 cells in the presence of phosphodiesterase inhibitors (PDEis) that prevent the breakdown of cyclic nucleotides, we found that prolonged ST intoxication induced extracellular cGMP accumulation in the presence or absence of PDEis. Further, ST intoxication induced luminal cGMP in vivo in mice, suggesting that secreted cGMP may have other cellular functions. Using transcriptome sequencing (RNA-seq) and quantitative PCR (qPCR), we demonstrated that ST intoxication, or treatment with the clinically used ST mimic linaclotide, altered inflammatory cytokine gene expression, including the interleukin 1 (IL-1) family member IL-33, which could also be induced by cell-permeative 8-Br-cGMP. Finally, when present during immunization, ST suppressed induction of antibodies to specific antigens. In conclusion, our studies indicate that ST modulates epithelial cell physiology and the interplay between the epithelial and immune compartments.

Metagenomic Next-Generation Sequencing for Pathogen Detection and Transcriptomic Analysis in Pediatric Central Nervous System Infections.

BackgroundPediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management and in characterizing prognosis. Usual care testing by culture and polymerase chain reaction is often unable to identify a pathogen. We examined the systematic application of metagenomic next-generation sequencing (mNGS) for detecting organisms and transcriptomic analysis of cerebrospinal fluid (CSF) in children with central nervous system (CNS) infections.MethodsWe conducted a prospective multisite study that aimed to enroll all children with a CSF pleocytosis and suspected CNS infection admitted to 1 of 3 tertiary pediatric hospitals during the study timeframe. After usual care testing had been performed, the remaining CSF was sent for mNGS and transcriptomic analysis.ResultsWe screened 221 and enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 25 (35.7%) subjects by any diagnostic modality. Metagenomic next-generation sequencing of the CSF samples identified a pathogen in 20 (28.6%) subjects, which were also all identified by usual care testing. The median time to result was 38 hours.ConclusionsMetagenomic sequencing of CSF has the potential to rapidly identify pathogens in children with CNS infections.

Etiology of Lower Respiratory Tract Infections in Children Requiring Mechanical Ventilation: A Multicenter Prospective Surveillance Study Incorporating Airway Metagenomics

Background: Lower respiratory tract infections (LRTI) are a leading cause of mortality in children with critical illness. Despite this, the pathogenic microbes in this vulnerable demographic frequently remain unknown. Metagenomic next generation sequencing (mNGS) can complement traditional diagnostics in epidemiologic surveillance studies by providing broad-range pathogen detection. Methods: We conducted a prospective, multicenter cohort study of critically ill children ages 31 days to 17 years with respiratory failure requiring prolonged mechanical ventilation. Using a combination of clinically-ordered testing and tracheal aspirate mNGS we determined the prevalence, seasonal variation, and genetic relatedness of respiratory pathogens in children with clinically adjudicated LRTI (n=276) or no LRTI (n=121). Findings: A presumptive microbiologic etiology was identified in 92% of children, with RSV (46%), Haemophilus influenzae (25%) and Moraxella catarrhalis (24%) being most common. mNGS identified uncommon pathogens including Ureaplasma parvum (<1%) and Bocavirus (3%). Co-detection of viral and bacterial pathogens occurred in 52% of cases. Incidental carriage of potentially pathogenic microbes was observed in 68% of children without LRTI, with rhinovirus (25%) most prevalent. RSV, H. influenzae and M. catarrhalis were statistically more prevalent in children under five. Both viral and bacterial LRTI occurred predominantly during winter months, and RSV infection was characterized by seasonal and geographic clusters of related strains. Interpretation: The combination of clinical diagnostics and mNGS enabled comprehensive pathogen surveillance in critically ill children with LRTI. RSV, H. influenzae , and M. catarrhalis were disproportionately represented. Carriage of potentially pathogenic microbes was common in children without LRTI. Funding Statement: NIH, Chan Zuckerberg Biohub Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The study was approved by a central IRB at the University of Utah.

Genetic diversity of Parechovirus A in infants and children with acute gastroenteritis in Japan during 2016-2018.

Parechovirus A (PeV-A), previously known as human parechovirus, is a common pathogen in children that can cause respiratory and gastrointestinal diseases as well as severe neurological disease. Take advantage of our previous findings on the genetic diversity of PeV-A circulating in Japanese children with acute gastroenteritis (AGE), this study was conducted to investigate the genetic diversity of PeV-A isolated from children with AGE in Japan as well as their clinical symptoms. Of 1070 stool samples collected from Japanese infants and children with AGE during the 2-year period from July 2016 to June 2018, 76 were positive for PeV-A by multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) and were subjected to genotyping based on viral protein 1 (VP1) sequences. Five different PeV-A genotypes including PeV-A1B, -A2, -A3, -A4, and -A6 were detected with predominant of PeV-A1 clade B genotype. This study revealed a high genetic diversity of PeV-A circulating in Japanese infants and children with AGE and the PeV-A2, a rare genotype, was detected for the first time in Japan in patients with AGE. The clinical symptoms observed in these patients included diarrhea, vomiting, fever, cough, rhinorrhea, and dehydration.

Rising resistance of urinary tract pathogens in children: a cause for concern.

Urinary tract infection (UTI) is one of the common infections in childhood. Prompt diagnosis and treatment reduces the risk of complications. The choice of antibiotic to treat UTI varies from region to region. Rational use and appropriately chosen antibiotic reduces the emergence of resistant uropathogens. We investigated the resistance pattern of uropathogens for commonly used antibiotics to treat UTI locally. Data was collected between 2009 and 2019 on all infants and children under 16 years of age with culture proven UTI. Results were compared with previously published figures between 2002 and 2008. A total of 1002 samples were analysed (91/year). Male to female ratio was 1:4.6. About 94% of the samples grew E. coli. As before, high resistance rates were recorded to Amoxicillin and Trimethoprim (Z=-0.325: P=0.7452; not significant). Overall, average resistance has decreased for Nitrofurantoin from 10% between 2002 and 2008 to 5.84% between 2009 and 2019 (Z=3.002: P=0.0027). On the other hand, Cefalexin resistance has increased from 7.4 to 14.56% between the two study periods (Z=-4.2: P=<0.0002). Despite rising resistance rates, we recommend that Cefalexin should cautiously remain the antibiotic of choice for empirically treating uncomplicated urinary tract infections in secondary care pending urine culture. Nitrofurantoin should be reserved for treating non-coliform/atypical UTIs or multi-drug resistant UTIs. There is an ongoing need for clinicians in all geographic regions to continue to monitor antibiotic resistance rates every few years.

The Epidemiology, Molecular, and Clinical of Human Adenoviruses in Children Hospitalized With Acute Respiratory Infections.

IntroductionHuman adenovirus (HAdV) is a common pathogen in children with acute respiratory infections (ARIs). The aim was to describe the epidemiology, molecular, and clinical characteristics of HAdV among children hospitalized with ARIs in Wenzhou in southeastern China.MethodologyFrom January 2018 to December 2019, nasopharyngeal swab or sputum specimens were prospectively collected from hospitalized children with ARIs. HAdV was detected using direct immunofluorescence. We used a multiplex PCR assay combined with capillary electrophoresis targeting the hexon gene’s hypervariable region to identify HAdV types 1, 2, 3, 4, 5, 7, 14, 21, 37, 40, 41, and 55. We analyzed the epidemiological, molecular, and clinical data according to the HAdV type.ResultsHAdVs were detected in 1,059 (3.5%) of the total of 30,543 children tested. A total of 947 cases with monotype HAdV identified by the PCR assay were included in the analysis. HAdV-3 (415/947, 43.8%), HAdV-7 (318/947, 33.6%), HAdV-2 (108/947, 11.4%), and HAdV-1 (70/947, 7.4%) were the predominant types. Of the 550 (58.1%) cases detected from December 2018 to August 2019, HAdV-3, and HAdV-7 were the main types. The main diagnoses included 358 cases of pneumonia, 232 cases of tonsillitis, 198 cases of bronchitis, and 159 cases of upper respiratory tract infection (URTI). Among children with pneumonia the main types were HAdV-7 (51.1%), HAdV-3 (36.9%), and HAdV-1 (2.2%). Among children with bronchitis, the main types were HAdV-3 (48.0%), HAdV-7 (28.3%), and HAdV-2 (10.6%). Among children with URTIs, the main types were HAdV-3 (49.7%), HAdV-7 (22.6%), and HAdV-2 (13.2%). Among children with tonsillitis, the main types were HAdV-3 (47.4%), HAdV-2 (22.4%), and HAdV-7 (18.5%). In total, 101 (55.2%) patients required supplemental oxygen, 15 (8.2%) required critical care, and 1 child (0.5%) with HAdV-7 pneumonia died.ConclusionHAdV-3 -7, -2, and -1 were the predominant types identified in hospitalized children with ARIs in Wenzhou. From December 2018 to August 2019, there were outbreaks of HAdV-3 and -7. There were significant differences in HAdV types among children with pneumonia, tonsillitis, bronchitis, and URTI. HAdV-7 can cause more severe pneumonia in children than HAdV-3.