SARS-CoV-2 immune repertoire in MIS-C and pediatric COVID-19.

There is limited understanding of the viral antibody fingerprint following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children. Herein, SARS-CoV-2 proteome-wide immunoprofiling of children with mild/moderate or severe coronavirus disease 2019 (COVID-19) versus multisystem inflammatory syndrome in children versus hospitalized control patients revealed differential cytokine responses, IgM/IgG/IgA epitope diversity, antibody binding and avidity. Apart from spike and nucleocapsid, IgG/IgA recognized epitopes in nonstructural protein (NSP) 2, NSP3, NSP12-NSP14 and open reading frame (ORF) 3a-ORF9. Peptides representing epitopes in NSP12, ORF3a and ORF8 demonstrated SARS-CoV-2 serodiagnosis. Antibody-binding kinetics with 24 SARS-CoV-2 proteins revealed antibody parameters that distinguish children with mild/moderate versus severe COVID-19 or multisystem inflammatory syndrome in children. Antibody avidity to prefusion spike correlated with decreased illness severity and served as a clinical disease indicator. The fusion peptide and heptad repeat 2 region induced SARS-CoV-2-neutralizing antibodies in rabbits. Thus, we identified SARS-CoV-2 antibody signatures in children associated with disease severity and delineate promising serodiagnostic and virus neutralization targets. These findings might guide the design of serodiagnostic assays, prognostic algorithms, therapeutics and vaccines in this important but understudied population.

Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM).

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by experts in both adult and pediatric laboratory and clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including arboviral Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also addressed. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

The burden of respiratory syncytial virus infections among children with sickle cell disease.

BACKGROUND: Although respiratory syncytial virus (RSV) is the leading cause of pediatric lower respiratory tract infections, the burden of RSV in children with sickle cell disease (SCD) is unknown. METHODS: We conducted a retrospective, nested, case-control study of children with SCD <18 years who had respiratory viral panels (RVPs) performed at Children's Healthcare of Atlanta from 2012 to 2019. We abstracted the medical records to describe the demographics, clinical features, and outcomes of children who tested positive for RSV (cases) versus children who tested negative (controls). We calculated the annual incidence of RSV and related hospitalization rates with 95% confidence intervals (CIs) and used multivariate logistic regression to evaluate associations. RESULTS: We identified 3676 RVP tests performed on 2636 patients over seven respiratory seasons resulting in 219/3676 (6.0%) RSV-positive tests among 160/2636 (6.1%) patients. The average annual incidence of laboratory-confirmed RSV infection among children with SCD was 34.3 (95% CI 18.7-49.8) and 3.8 (95% CI 0.5-7.0) cases per 1000 person-years for those <5 years and 5-18 years, respectively. The RSV-related hospitalization rate for children <5 years was 20.7 (95% CI 8.5-32.8) per 1000 person-years. RSV-positive cases were significantly younger than RSV-negative patients (3.8 years vs 7.6 years, P < .001). Of RSV-positive cases, 22 (13.8%) developed acute chest syndrome and nine (5.6%) required intensive care, which was not significantly different from RSV-negative children with SCD. CONCLUSION: RSV infections are common in children with SCD with higher burden in younger patients. RSV is associated with considerable morbidity, including higher rates of hospitalization compared to the general population.

Practical Guidance for Clinical Microbiology Laboratories: Viruses Causing Acute Respiratory Tract Infections.

Respiratory viral infections are associated with a wide range of acute syndromes and infectious disease processes in children and adults worldwide. Many viruses are implicated in these infections, and these viruses are spread largely via respiratory means between humans but also occasionally from animals to humans. This article is an American Society for Microbiology (ASM)-sponsored Practical Guidance for Clinical Microbiology (PGCM) document identifying best practices for diagnosis and characterization of viruses that cause acute respiratory infections and replaces the most recent prior version of the ASM-sponsored Cumitech 21 document, Laboratory Diagnosis of Viral Respiratory Disease, published in 1986. The scope of the original document was quite broad, with an emphasis on clinical diagnosis of a wide variety of infectious agents and laboratory focus on antigen detection and viral culture. The new PGCM document is designed to be used by laboratorians in a wide variety of diagnostic and public health microbiology/virology laboratory settings worldwide. The article provides guidance to a rapidly changing field of diagnostics and outlines the epidemiology and clinical impact of acute respiratory viral infections, including preferred methods of specimen collection and current methods for diagnosis and characterization of viral pathogens causing acute respiratory tract infections. Compared to the case in 1986, molecular techniques are now the preferred diagnostic approaches for the detection of acute respiratory viruses, and they allow for automation, high-throughput workflows, and near-patient testing. These changes require quality assurance programs to prevent laboratory contamination as well as strong preanalytical screening approaches to utilize laboratory resources appropriately. Appropriate guidance from laboratorians to stakeholders will allow for appropriate specimen collection, as well as correct test ordering that will quickly identify highly transmissible emerging pathogens.

Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs.

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 asymptomatic versus 197 symptomatic children aged 0 to 4 years, 79 asymptomatic versus 97 symptomatic children aged 5 to 9 years, 69 asymptomatic versus 75 symptomatic children aged 10 to 13 years, 73 asymptomatic versus 109 symptomatic children aged 14 to 17 years) were compared. The median adjusted Ct value for asymptomatic children was 10.3 cycles higher than for symptomatic children (P < 0.0001), and VL were 3 to 4 logs lower than for symptomatic children (P < 0.0001); differences were consistent (P < 0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (odds ratio [OR], 6.5; P = 0.01), a recent contact (OR, 2.3; P = 0.02), and testing for surveillance (OR, 2.7; P = 0.005) had higher estimated risks of having a Ct value in the lowest quartile than children without, while an immunocompromised status had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in their nasopharynx/oropharynx than symptomatic children, but the timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.

Microbiology and radiographic features of osteomyelitis in children and adolescents with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for bacterial infections including osteomyelitis (OM). Fever and bone pain, key presenting symptoms of OM, are common in SCD, thus complicating diagnosis. We reviewed presentation, imaging features, and microbiologic etiologies of children with SCD treated for OM. METHODS: The comprehensive SCD clinical database of children and adolescents with SCD followed at a single, large tertiary pediatric center were searched to identify all diagnostic coding for potential cases of osteomyelitis in children ages 6 months to 21 years from 2010 to 2019. Medical charts were reviewed to determine OM diagnostic probability based on radiographic and microbiologic findings and the duration of prescribed antibiotic treatment for OM. RESULTS: Review of 3553 patients (18 039 person-years) identified 20 episodes of probable OM in 19 children. Magnetic resonance imaging (MRI) findings to support OM were definitive in 4/19 (21%), probable in 10/19 (53%), suspected in 5/19 (26%), based on blinded radiologist review. Blood and/or operative cultures from bone and tissue debridement isolated Salmonella species in seven (35%) cases and methicillin-susceptible Staphylococcus aureus (MSSA) in two (10%). Six patients received antibiotic treatment prior to obtainment of cultures. Of culture-positive cases, MRI findings for OM were definitive or probable in six of nine (67%), suspected in three of nine (33%). CONCLUSIONS: Distinction between OM and sickle-related bone infarct or vasoocclusion is difficult based on imaging findings alone. Early attainment of blood and operative cultures increases the likelihood of identifying and adequately treating OM.

Influenza vaccine effectiveness and disease burden in children and adolescents with sickle cell disease: 2012-2017.

BACKGROUND: Data are limited on the burden of influenza and seasonal influenza vaccine effectiveness (VE) in children with sickle cell disease (SCD). METHODS: We used a prospectively collected clinical registry of SCD patients 6 months to 21 years of age to determine the influenza cases per 100 patient-years, vaccination rates, and a test-negative case-control study design to estimate influenza VE against medically attended laboratory-confirmed influenza infection. Influenza-positive cases were randomly matched to test-negative controls on age and influenza season in 1:1 ratio. We used adjusted logistic regression models to compare odds ratio (OR) of vaccination in cases to controls. We calculated VE as [100% × (1 - adjusted OR)] and computed 95% confidence intervals (CIs) around the estimate. RESULTS: There were 1037 children with SCD who were tested for influenza, 307 children (29.6%) had at least one influenza infection (338 infections, incidence rate 3.7 per 100 person-years; 95% CI, 3.4-4.1) and 56.2% of those tested received annual influenza vaccine. Overall VE pooled over five seasons was 22.3% (95% CI, -7.3% to 43.7%). Adjusted VE estimates ranged from 39.7% (95% CI, -70.1% to 78.6%) in 2015/2016 to -5.9% (95% CI, -88.4% to 40.4%) in the 2016/17 seasons. Influenza VE varied by age and was highest in children 1-5 years of age (66.6%; 95% CI, 30.3-84.0). Adjusted VE against acute chest syndrome during influenza infection was 39.4% (95% CI, -113.0 to 82.8%). CONCLUSIONS: Influenza VE in patients with SCD varies by season and age. Multicenter prospective studies are needed to better establish and monitor influenza VE among children with SCD.

Incidence of invasive Haemophilus influenzae infections in children with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for invasive infection with encapsulated bacteria. Antibiotic prophylaxis and immunizations against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) have decreased the overall incidence of invasive infections and have shifted distribution of serotypes causing disease toward those not covered by immunizations. We sought to determine the current incidence of invasive H. influenzae infections in children with SCD and to describe the clinical features and management of these infections. METHODS: Microbiology reports of a large pediatric tertiary care center were reviewed to identify all isolates of H. influenzae detected in sterile body fluid cultures from January 1, 2010 to December 31, 2017. Results were compared with the center's comprehensive clinical database of all children with SCD to identify all cases of children ages 0 to18 years with SCD with invasive H. influenzae disease for the same time period. RESULTS: We captured 2444 patients with SCD, with 14,336 person-years. There were eight episodes of H. influenzae bacteremia in seven children with SCD (five type f, two non-typable, one type a). Most episodes (7 of 8) were in children < 5 years. The incidence rate of invasive H. influenzae in SCD was 0.58/1000 person-years for ages 0 to 18 years and 1.60/1000 person-years for children age < 5 years. There were no deaths from H. influenzae infection. CONCLUSIONS: In the era of universal antibiotic prophylaxis and immunization against Hib, invasive H. influenzae disease due to nonvaccine serotypes remains a risk for children with SCD, particularly those under five years of age.

Correction to: Geographic surveillance of community associated MRSA infections in children using electronic health record data.

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Geographic surveillance of community associated MRSA infections in children using electronic health record data.

BACKGROUND: Community- associated methicillin resistant Staphylococcus aureus (CA-MRSA) cause serious infections and rates continue to rise worldwide. Use of geocoded electronic health record (EHR) data to prevent spread of disease is limited in health service research. We demonstrate how geocoded EHR and spatial analyses can be used to identify risks for CA-MRSA in children, which are tied to place-based determinants and would not be uncovered using traditional EHR data analyses. METHODS: An epidemiology study was conducted on children from January 1, 2002 through December 31, 2010 who were treated for Staphylococcus aureus infections. A generalized estimated equations (GEE) model was developed and crude and adjusted odds ratios were based on S. aureus risks. We measured the risk of S. aureus as standardized incidence ratios (SIR) calculated within aggregated US 2010 Census tracts called spatially adaptive filters, and then created maps that differentiate the geographic patterns of antibiotic resistant and non-resistant forms of S. aureus. RESULTS: CA-MRSA rates increased at higher rates compared to non-resistant forms, p = 0.01. Children with no or public health insurance had higher odds of CA-MRSA infection. Black children were almost 1.5 times as likely as white children to have CA-MRSA infections (aOR 95% CI 1.44,1.75, p < 0.0001); this finding persisted at the block group level (p < 0.001) along with household crowding (p < 0.001). The youngest category of age (< 4 years) also had increased risk for CA-MRSA (aOR 1.65, 95%CI 1.48, 1.83, p < 0.0001). CA-MRSA encompasses larger areas with higher SIRs compared to non-resistant forms and were found in block groups with higher proportion of blacks (r = 0.517, p < 0.001), younger age (r = 0.137, p < 0.001), and crowding (r = 0.320, p < 0.001). CONCLUSIONS: In the Atlanta MSA, the risk for CA-MRSA is associated with neighborhood-level measures of racial composition, household crowding, and age of children. Neighborhoods which have higher proportion of blacks, household crowding, and children < 4 years of age are at greatest risk. Understanding spatial relationship at a community level and how it relates to risks for antibiotic resistant infections is important to combat the growing numbers and spread of such infections like CA-MRSA.

A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology.

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.

A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology.

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.

Multicenter Evaluation of the ePlex Respiratory Pathogen Panel for the Detection of Viral and Bacterial Respiratory Tract Pathogens in Nasopharyngeal Swabs.

The performance of the new ePlex Respiratory Pathogen (RP) panel (GenMark Diagnostics) for the simultaneous detection of 19 viruses (influenza A virus; influenza A H1 virus; influenza A 2009 H1 virus; influenza A H3 virus; influenza B virus; adenovirus; coronaviruses [HKU1, OC43, NL63, and 229E]; human rhinovirus/enterovirus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; and respiratory syncytial virus [RSV] [RSV subtype A and RSV subtype B]) and 2 bacteria (Mycoplasma pneumoniae and Chlamydia pneumoniae) was evaluated. Prospectively and retrospectively collected nasopharyngeal swab (NPS) specimens (n = 2,908) were evaluated by using the ePlex RP panel, with the bioMérieux/BioFire FilmArray Respiratory Panel (BioFire RP) as the comparator method. Discordance analysis was performed by using target-specific PCRs and bidirectional sequencing. The reproducibility of the assay was evaluated by using reproducibility panels comprised of 6 pathogens. The overall agreement between the ePlex RP and BioFire RP results was >95% for all targets. Positive percent agreement with the BioFire RP result for viruses ranged from 85.1% (95% confidence interval [CI], 80.2% to 88.9%) to 95.1% (95% CI, 89.0% to 97.9%), while negative percent agreement values ranged from 99.5% (95% CI, 99.1% to 99.7%) to 99.8% (95% CI, 99.5% to 99.9%). Additional testing of discordant targets (12%; 349/2,908) confirmed the results of ePlex RP for 38% (131/349) of samples tested. Reproducibility was 100% for all targets tested, with the exception of adenovirus, for which reproducibilities were 91.6% at low virus concentrations and 100% at moderate virus concentrations. The ePlex RP panel offers a new, rapid, and sensitive "sample-to-answer" multiplex panel for the detection of the most common viral and bacterial respiratory pathogens.

Sustained Effectiveness of Monovalent and Pentavalent Rotavirus Vaccines in Children.

OBJECTIVE: Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose monovalent rotavirus vaccine (RV1) and 3-dose pentavalent rotavirus vaccine (RV5) series given in infancy against rotavirus disease resulting in hospital emergency department or inpatient care. STUDY DESIGN: Children were eligible for enrollment if they presented to any 1 of 3 hospitals in Atlanta, Georgia with diarrhea ≤10 days duration during January-June 2013 and were born after RV1 introduction. Stool samples were tested for rotavirus by enzyme immunoassay and immunization records were obtained from providers and the state electronic immunization information system. Case-subjects (children testing rotavirus antigen-positive) were compared with children testing rotavirus antigen-negative. RESULTS: Overall, 98 rotavirus-case subjects and 175 rotavirus-negative controls were enrolled. Genotype G12P[8] predominated (n = 87, 89%). The VE of 2 RV1 doses was 84% (95% CI 38, 96) among children aged 8-23 months and 82% (95% CI 41, 95) among children aged ≥24 months. For the same age groups, the VE of 3 RV5 doses was 80% (95% CI 27, 95) and 87% (95% CI 22, 98), respectively. CONCLUSIONS: Under routine use, the RV1 and RV5 series were both effective against moderate-to-severe rotavirus disease during a G12P[8] season, and both vaccines demonstrated sustained protection beyond the first 2 years of life.

Candida quercitrusa Candidemia in a 6-Year-Old Child.

We present the first case of candidemia due to Candida quercitrusa in a pediatric patient. The identification of the isolate was protracted and ultimately dependent upon sequence analysis of the internal transcribed spacer region. To further define the antifungal susceptibility characteristics of this species, we performed antifungal susceptibility testing of clinical and type strains. In light of the antifungal susceptibility testing results, we caution against the use of fluconazole for treating C. quercitrusa infections.

Multiplex viral polymerase chain reaction testing using the FilmArray device compared with direct fluorescent antibody testing.

Advances in fluidics, electronics, and instrument design have enabled automation of complex molecular assays. The FilmArray Respiratory Panel (RP) is one such assay; it allows for rapid detection of multiple viral and bacterial respiratory targets via nested polymerase chain reaction (PCR), with all components contained within a single pouch. We performed a detailed comparison of workflow between the FilmArray RP and direct fluorescent antibody (DFA) staining. The FilmArray RP proved to be more efficient, with as few as 91 total touches needed and as little as 4 minutes 52 seconds hands-on time. This compares with as many as 502 total touches and 12 minutes 45 seconds hands-on time for DFA staining. FilmArray RP detected a greater number of organisms (20 viruses and bacteria vs 7 viruses for DFA staining) and required less training compared with DFA staining. The ease of use of the FilmArray RP makes this molecular assay amenable to operation 24 hours a day, 7 days a week in routine laboratory and point-of-care settings.

Bloodstream Infections in Children With Sickle Cell Disease: 2010-2019.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for bloodstream infections (BSIs), mainly because of functional asplenia. Immunizations and antibiotic prophylaxis have reduced the prevalence of invasive bacterial infections, but contemporary analysis of BSI in children with SCD is limited. METHODS: We conducted a retrospective cohort study of children aged <18 years with SCD who had blood cultures collected at our institution from 2010 to 2019 to identify BSI. Probable contaminant organisms were identified and not included as BSI. We calculated the annual incidence of BSI at our institution with 95% confidence intervals (CIs) and used multivariate logistic regression to evaluate associations. RESULTS: There were 2694 eligible patients with 19 902 blood cultures. Excluding repeated cultures and contaminant cultures, there were 156 BSI episodes in 144 patients. The median age at BSI was 7.5 years. The average incidence rate of BSI was 0.89 per 100 person-years (95% CI 0.45-1.32). The most common pathogens were Streptococcus pneumoniae (16.0%), Streptococcus viridans group (9.0%), Escherichia coli (9.0%), Staphylococcus aureus (7.7%), Bordetella holmesii (7.7%), Haemophilus influenzae (7.1%), and Salmonella species (6.4%). Odds of BSI were higher with sickle cell anemia genotypes (odds ratio [OR] 1.88; 95% CI 1.20-2.94) and chronic transfusions (OR 2.66; 95% CI 1.51-4.69) and lower with hydroxyurea (OR 0.57; 95% CI 0.39-0.84). CONCLUSIONS: BSI remains a risk for children with SCD. Overall incidence, risk factors, and spectrum of pathogens are important considerations to guide prevention and empirical treatment of suspected infection in SCD.

Rotavirus Strain Trends in United States, 2009-2016: Results from the National Rotavirus Strain Surveillance System (NRSSS).

Before the introduction of vaccines, group A rotaviruses (RVA) were the leading cause of acute gastroenteritis in children worldwide. The National Rotavirus Strain Surveillance System (NRSSS) was established in 1996 by the Centers for Disease Control and Prevention (CDC) to perform passive RVA surveillance in the USA. We report the distribution of RVA genotypes collected through NRSSS during the 2009-2016 RVA seasons and retrospectively examine the genotypes detected through the NRSSS since 1996. During the 2009-2016 RVA seasons, 2134 RVA-positive fecal specimens were sent to the CDC for analysis of the VP7 and VP4 genes by RT-PCR genotyping assays and sequencing. During 2009-2011, RVA genotype G3P[8] dominated, while G12P[8] was the dominant genotype during 2012-2016. Vaccine strains were detected in 1.7% of specimens and uncommon/unusual strains, including equine-like G3P[8] strains, were found in 1.9%. Phylogenetic analyses showed limited VP7 and VP4 sequence variation within the common genotypes with 1-3 alleles/lineages identified per genotype. A review of 20 years of NRSSS surveillance showed two changes in genotype dominance, from G1P[8] to G3P[8] and then G3P[8] to G12P[8]. A better understanding of the long-term effects of vaccine use on epidemiological and evolutionary dynamics of circulating RVA strains requires continued surveillance.