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1.
Clin Infect Dis ; 78(3): 573-581, 2024 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-38097379

RESUMEN

BACKGROUND: Multiplex molecular diagnostic panels have greatly enhanced detection of gastrointestinal pathogens. However, data on the impact of these tests on clinical and patient-centered outcomes are limited. METHODS: We conducted a prospective, multicenter, stepped-wedge trial to determine the impact of multiplex molecular testing at 5 academic children's hospitals on children presenting to the emergency department with acute gastroenteritis. Caregivers were interviewed on enrollment and 7-10 days after enrollment to determine symptoms, risk factors, subsequent medical visits, and impact on family members. During the pre-intervention period, diagnostic testing was performed at the clinician's discretion . During the intervention period, multiplex molecular testing was performed on all children, with results available to clinicians. The primary outcome was return visits to a healthcare provider within 10 days of enrollment. RESULTS: Potential pathogens were identified by clinician-ordered tests in 19 of 571 (3.3%) in the pre-intervention period compared with 434 of 586 (74%) in the intervention period; clinically relevant pathogens were detected in 2.1% and 15%, respectively. In the multivariate model, the intervention was associated with a 21% reduction in the odds of any return visit (odds ratio, 0.79; 95% confidence interval, .70-.90) after adjusting for potential confounders. Appropriate treatment was prescribed in 11.3% compared with 19.6% during the intervention period (P = .22). CONCLUSIONS: Routine molecular multiplex testing for all children who presented to the ED with acute gastroenteritis detected more clinically relevant pathogens and led to a 21% decrease in return visits. Additional research is needed to define patients most likely to benefit from testing. Clinical Trials Registration. NCT02248285.


Asunto(s)
Gastroenteritis , Niño , Humanos , Servicio de Urgencia en Hospital , Gastroenteritis/diagnóstico , Gastroenteritis/tratamiento farmacológico , Técnicas de Diagnóstico Molecular/métodos , Estudios Prospectivos , Factores de Riesgo
2.
J Clin Microbiol ; : e0035924, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904385

RESUMEN

Medical microbiologists, defined as doctoral-level laboratory directors with subspecialty training in medical microbiology, lead the clinical laboratory operations through activities such as clinical consultations, oversight of diagnostic testing menu, institutional leadership, education, and scholastic activities. However, unlike their clinical colleagues, medical microbiologists are largely unable to bill for clinical consultations performed within the hospital and, therefore, unable to generate relative value units or a similar quantifiable metric. As hospital budgets tighten and justification of staffing becomes a necessity, this may present a challenge to the medical microbiologist attempting to prove their value to the organization. To aid in providing tangible data, the Personnel Standards and Workforce subcommittee of the American Society for Microbiology conducted a multi-center study across seven medical centers to document clinical consultations and their impact. Consults were generated equally from internal (laboratory-based) and external (hospital-based) parties, with the majority directly impacting patient management. Near universal acceptance of the medical microbiologist's recommendation highlights the worth derived from their expertise. External consults required more time commitment from the medical microbiologist than internal consults, although both presented ample opportunity for secondary value, including impact through stewardship, education, clinical guidance, and cost reduction. This study is a description of the content and impact of consultations that underscore the importance of the medical microbiologist as a key member of the healthcare team. IMPORTANCE: Medical microbiologists are invaluable to the clinical microbiology laboratory and the healthcare system as a whole. However, as medical microbiologists do not regularly generate relative value units, capturing and quantifying the value provided is challenging. As hospital budgets tighten, justification of staffing becomes a necessity. To aid in providing tangible data, the Personnel Standards and Workforce subcommittee of the American Society for Microbiology conducted a multi-center study across seven medical centers to document clinical consultations and their impact. To our knowledge, this is the first study to provide detailed evaluation of the consultative value provided by medical microbiologists.

3.
J Pediatr ; 259: 113419, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37044372

RESUMEN

OBJECTIVES: To evaluate implementation of rifamycin-based regimens (RBR) for pediatric tuberculosis infection (TBI) treatment among 3 provider settings in a high-incidence county. STUDY DESIGN: A multicenter, retrospective observational study was performed across 3 sites in Los Angeles County: an academic center (AC), a general pediatrics federally qualified health center (FQHC), and department of public health (DPH) tuberculosis clinics. Patients initiated on TBI treatment age 1 months to 17 years between 2018 and 2020 were included. RBRs were defined as regimens: 3 months of weekly rifapentine and isoniazid, 4 months of daily rifampin, and 3 months of daily isoniazid and rifampin. RESULTS: We included 424 patients: 51 from AC, 327 from DPH, and 46 from FQHC. RBR use nearly doubled during the study period (from 43% in 2018 to 82% in 2020; P < .001). FQHC had the shortest time to chest radiograph and treatment initiation; however, AC and DPH were 4 times as likely to prescribe an RBR compared to FQHC (95% CI, 2.1-7.8). AC and DPH had similar completion rates (74%) and were 2.6 times as likely to complete treatment compared to FQHC (95% CI, 1.4-4.9). CONCLUSIONS: The use of RBRs for pediatric TBI varies significantly by clinical setting but is improving over time. Strategies are needed to improve RBR uptake, standardize care, and increase treatment completion, particularly among general pediatricians.


Asunto(s)
Tuberculosis Latente , Pediatría , Tuberculosis , Humanos , Niño , Lactante , Rifampin/uso terapéutico , Isoniazida/uso terapéutico , Antituberculosos/uso terapéutico , Tuberculosis/tratamiento farmacológico , Quimioterapia Combinada
4.
J Clin Microbiol ; 59(1)2020 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-33093026

RESUMEN

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.


Asunto(s)
Infecciones Asintomáticas/epidemiología , COVID-19/diagnóstico , COVID-19/epidemiología , Carga Viral , Adolescente , Prueba de COVID-19/métodos , Niño , Preescolar , Femenino , Hospitales Pediátricos , Humanos , Lactante , Recién Nacido , Masculino , Nasofaringe/virología , Orofaringe/virología , SARS-CoV-2/aislamiento & purificación
5.
Curr Opin Pediatr ; 30(1): 125-130, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29189352

RESUMEN

PURPOSE OF REVIEW: With the advent of novel massively parallel sequencing technologies and bioinformatic processing capabilities, clinical applications of metagenomic studies are rapidly being integrated into medicine. Through this paper, we hope to introduce this powerful new tool to clinicians caring for children. RECENT FINDINGS: Very few studies have looked at metagenomic applications in children. The ability to perform these types of massive sequencing projects was not possible as little as 7 years ago. SUMMARY: Metagenomics is defined as the study of all genetic material within a given sample. Novel sequencing and analysis approaches allow for unbiased assays to identify pathogens missed by targeted sequencing and culture methods. Although not widely available yet, metagenomic studies have been used to diagnose pediatric infections, identify resistance genes in clinical samples, and characterize outbreaks. Although cost and turnaround time have limited its application in clinical laboratories to date, novel platforms and increasing comfort with these techniques continue to push diagnostic metagenomics into clinical pediatric medicine. Much work in this field is yet to be done. That being said, we feel that pediatric clinicians will be using metagenomic techniques in the care of children with increasing frequency in the near future.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Infecciones/diagnóstico , Metagenómica , Niño , Humanos , Infecciones/microbiología , Pediatría
6.
J Clin Microbiol ; 54(7): 1789-1796, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27098961

RESUMEN

Gram-negative bacteremia is highly fatal, and hospitalizations due to sepsis have been increasing worldwide. Molecular tests that supplement Gram stain results from positive blood cultures provide specific organism information to potentially guide therapy, but more clinical data on their real-world impact are still needed. We retrospectively reviewed cases of Gram-negative bacteremia in hospitalized patients over a 6-month period before (n = 98) and over a 6-month period after (n = 97) the implementation of a microarray-based early identification and resistance marker detection system (Verigene BC-GN; Nanosphere) while antimicrobial stewardship practices remained constant. Patient demographics, time to organism identification, time to effective antimicrobial therapy, and other key clinical parameters were compared. The two groups did not differ statistically with regard to comorbid conditions, sources of bacteremia, or numbers of intensive care unit (ICU) admissions, active use of immunosuppressive therapy, neutropenia, or bacteremia due to multidrug-resistant organisms. The BC-GN panel yielded an identification in 87% of Gram-negative cultures and was accurate in 95/97 (98%) of the cases compared to results using conventional culture. Organism identifications were achieved more quickly post-microarray implementation (mean, 10.9 h versus 37.9 h; P < 0.001). Length of ICU stay, 30-day mortality, and mortality associated with multidrug-resistant organisms were significantly lower in the postintervention group (P < 0.05). More rapid implementation of effective therapy was statistically significant for postintervention cases of extended-spectrum beta-lactamase-producing organisms (P = 0.049) but not overall (P = 0.12). The Verigene BC-GN assay is a valuable addition for the early identification of Gram-negative organisms that cause bloodstream infections and can significantly impact patient care, particularly when resistance markers are detected.


Asunto(s)
Bacteriemia/diagnóstico , Cultivo de Sangre , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/diagnóstico , Análisis por Micromatrices/métodos , Técnicas de Diagnóstico Molecular/métodos , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Precoz , Femenino , Bacterias Gramnegativas/genética , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Prevención Secundaria , Factores de Tiempo , Adulto Joven
8.
J Clin Lab Anal ; 28(5): 349-52, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24648198

RESUMEN

BACKGROUND: Human rhinovirus (HRV) is a common cause of respiratory illness in children. The impact of HRV infection on 1- to 90-day-old infants is unclear. We hypothesized that HRV infection would be clinically similar to respiratory syncytial virus (RSV) infection in the hospitalized infants. METHODS: We conducted a retrospective study of hospitalized infants, who were 1-90 days old, with HRV or RSV within the Southern California Kaiser Permanente network over a 1-year period (August 2010 to October 2011). RESULTS: We identified 245 hospitalized infants who underwent respiratory virus testing. HRV was found in 52 infants (21%) compared to 79 infants (32%) with RSV (P = 0.008). Infants with HRV infection experienced longer hospital stays compared to those with RSV (median length of stay 4 days vs. 3 days, P = 0.009) and had fewer short hospital stays ≤3 days (P = 0.029). There was a trend in infants with HRV infection to be younger (P = 0.071) and have more fevers (P = 0.052). CONCLUSIONS: Recent advances in diagnostics allow for identification of a broad range of viral pathogens in infants. Compared to RSV, HRV was associated with longer hospital stays. Additional studies and improved, more specific testing, methods are needed to further define the effects of HRV infection in infants 1-90 days old.


Asunto(s)
Hospitalización/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Infecciones por Picornaviridae , Rhinovirus/patogenicidad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Infecciones por Picornaviridae/diagnóstico , Infecciones por Picornaviridae/epidemiología , Infecciones por Picornaviridae/terapia , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/terapia , Virus Sincitiales Respiratorios/patogenicidad , Estudios Retrospectivos
9.
Viruses ; 16(6)2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38932145

RESUMEN

Mucosal immunity may contribute to clearing SARS-CoV-2 infection prior to systemic infection, thereby allowing hosts to remain seronegative. We describe the meaningful detection of SARS-CoV-2-specific nasal mucosal antibodies in a group of exposed-household individuals that evaded systemic infection. Between June 2020 and February 2023, nasopharyngeal swab (NPS) and acute and convalescent blood were collected from individuals exposed to a SARS-CoV-2-confirmed household member. Nasal secretory IgA (SIgA) antibodies targeting the SARS-CoV-2 spike protein were measured using a modified ELISA. Of the 36 exposed individuals without SARS-CoV-2 detected by the RT-PCR of NPS specimens and seronegative for SARS-CoV-2-specific IgG at enrollment and convalescence, 13 (36.1%) had positive SARS-CoV-2-specific SIgA levels detected in the nasal mucosa at enrollment. These individuals had significantly higher nasal SIgA (median 0.52 AU/mL) compared with never-exposed, never-infected controls (0.001 AU/mL) and infected-family participants (0.0002 AU/mL) during the acute visit, respectively (both p < 0.001). The nasal SARS-CoV-2-specific SIgA decreased rapidly over two weeks in the exposed seronegative individuals compared to a rise in SIgA in infected-family members. The nasal SARS-CoV-2-specific SIgA may have a protective role in preventing systemic infection.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Inmunoglobulina A Secretora , Mucosa Nasal , SARS-CoV-2 , Humanos , SARS-CoV-2/inmunología , COVID-19/inmunología , COVID-19/diagnóstico , COVID-19/virología , Inmunoglobulina A Secretora/inmunología , Inmunoglobulina A Secretora/análisis , Masculino , Femenino , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Persona de Mediana Edad , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Mucosa Nasal/inmunología , Mucosa Nasal/virología , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto Joven , Inmunidad Mucosa , Anciano , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología
10.
medRxiv ; 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37577483

RESUMEN

Background: Multiplex molecular diagnostic panels have greatly enhanced detection of gastrointestinal pathogens. However, data on the impact of these tests on clinical and patient-centered outcomes are limited. Methods: We conducted a prospective, multicenter, stepped-wedge trial to determine the impact of multiplex molecular testing at five academic children's hospitals in children presenting to the ED with acute gastroenteritis. Caregivers were interviewed on enrollment and again 7-10 days after enrollment to determine symptoms, risk factors, subsequent medical visits, and impact on family members. During the pre-intervention period, diagnostic testing was performed at the discretion of clinicians. During the intervention period, multiplex molecular testing was performed on all children with results available to clinicians. Primary outcome was return visits to a health care provider within 10 days of enrollment. Results: Potential pathogens were identified by clinician ordered tests in 19/571 (3.3%) in the pre-intervention period compared to 434/586 (74%) in the intervention period; clinically relevant pathogens were detected in 2.1% and 15% respectively. In the multivariate model adjusting for potential confounders, the intervention was associated with a 21% reduction in the odds of any return visit (OR 0.79; 95% CI 0.70-0.90). Appropriate treatment was prescribed in 11.3% compared to 19.6% during the intervention period(P=0.22). Conclusions: Routine molecular multiplex testing for all children presenting to the ED with AGE detected more clinically relevant pathogens and led to a 21% decrease in return visits. Additional research is needed to define patients most likely to benefit from testing.

11.
Front Nutr ; 9: 898849, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35685893

RESUMEN

Infants remain at high risk for severe coronavirus disease 2019 (COVID-19). Human milk contains high levels of protective SARS CoV-2 specific antibodies post-infection and primary vaccine series, but levels decline over time. We hypothesized that the COVID-19 booster vaccine augment antibody production and the protection afforded to human milk-fed infants. We prospectively enrolled pregnant or lactating mothers planning to receive COVID-19 vaccination. We measured human milk IgG, IgA, and IgM antibodies targeting the SARS CoV-2 receptor binding domain within the spike protein and human milk neutralization activity against SARS CoV-2 in 10 lactating mothers from pre-COVID-19 primary series vaccine to post-booster dose. Human milk SARS CoV-2 specific IgG increased significantly from pre- to post-booster levels (median OD 0.33 vs. 2.02, P = 0.002). The IgG levels post-booster were even higher than the peak level after the primary series (2.02 vs. 0.95, P = 0.03). The increase in SARS CoV-2 specific IgA levels was not significant (0.10 vs. 0.33, P = 0.23). There was a strong correlation between paired maternal blood and milk IgG and IgA levels (IgG rho 0.52, P < 0.001, IgA rho 0.31, P = 0.05). Post-booster neutralizing activity was elevated compared to pre-booster levels (66% vs. 12% inhibition, P = 0.002). COVID-19 vaccine booster elicits SARS CoV-2 specific antibodies in human milk at higher levels compared to the initial primary series. This finding suggests that three doses of COVID-19 mRNA vaccination leads to improved mucosal response in human milk and reinforces current guidance recommending all pregnant or lactating mothers receive full COVID-19 vaccine courses with a booster dose.

12.
Emerg Infect Dis ; 17(9): 1645-50, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21888789

RESUMEN

Since the introduction of the Haemophilus influenzae type b vaccine, the incidence of invasive H. influenzae type b disease among children has fallen dramatically, but the effect on invasive H. influenzae disease among adults may be more complex. In this population-based study we examined the epidemiology and outcomes of invasive disease caused by typeable and nontypeable H. influenzae among Utah adults during 1998-2008. The overall incidence increased over the study period from 0.14/100,000 person-years in 1998 to 1.61/100,000 person-years in 2008. The average incidence in persons >65 years old was 2.74/100,000 person-years, accounting for 51% of cases and 67% of deaths. The incidence was highest for nontypeable H. influenzae (0.23/100,000 person-years), followed by H. influenzae type f (0.14/100,000 person-years). The case-fatality rate was 22%. The incidence of invasive H. influenzae in Utah adults appears to be increasing. Invasive H. influenzae infection disproportionately affected the elderly and was associated with a high mortality rate.


Asunto(s)
Bacteriemia/epidemiología , Infecciones por Haemophilus/epidemiología , Haemophilus influenzae/patogenicidad , Adolescente , Adulto , Anciano , Bacteriemia/microbiología , Bacteriemia/mortalidad , Infecciones por Haemophilus/microbiología , Infecciones por Haemophilus/mortalidad , Haemophilus influenzae/clasificación , Humanos , Incidencia , Meningitis por Haemophilus/epidemiología , Meningitis por Haemophilus/microbiología , Meningitis por Haemophilus/mortalidad , Persona de Mediana Edad , Serotipificación , Utah/epidemiología , Adulto Joven
14.
J Dev Behav Pediatr ; 42(8): 648-655, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34618722

RESUMEN

OBJECTIVE: Previous retrospective studies have examined elimination signals, stool toileting refusal, and completion age in Assisted Infant Toilet Training (AITT). The aim of this longitudinal cohort study was to describe the practice of AITT and caregiver satisfaction in a primarily Western setting during the first year of life. METHODS: Families who started AITT before 4 months of age were recruited. Standardized interviews of caregivers were conducted at 1- to 2-month intervals. To identify trends over time, data were fitted to a linear mixed-effect model. Data were analyzed according to five 2-month blocks, starting at 3 to 4 months. RESULTS: Of 85 participating families, 87 children started AITT at a mean age of 2.5 months. At all age intervals, 88% to 94% of caregivers could identify elimination signals. Toileting attempts decreased from 10/day at 3 to 4 months to 7/day at 11 to 12 months (p < 0.001). Many families (45%-53%) practiced AITT on a part-time basis. Daytime dryness was noted in 12% to 14% of infants throughout the first year. Although more than 63% of families used cloth or disposable diapers throughout this study, use of trainers and underwear increased significantly by 2- to 3-fold (p < 0.01 for both). Caregiver satisfaction was high overall. Although negatively associated with potty refusal, it was positively associated with daytime and nighttime dryness, perceived elimination signals, and a better understanding of their infant's needs (p < 0.001 for all). CONCLUSION: This study demonstrates that AITT is a worthy viable alternative to the use of diapers even in Western settings. Better understanding of AITT provides a new perspective to properly meet infants' basic needs.


Asunto(s)
Cuidadores , Control de Esfínteres , Niño , Humanos , Lactante , Estudios Longitudinales , Estudios Retrospectivos
15.
J Matern Fetal Neonatal Med ; 34(20): 3335-3343, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31744351

RESUMEN

INTRODUCTION: The infant gut microbiome is thought to play a key role in developing metabolic and immunologic pathways. Antibiotics have been shown to disrupt the human microbiome, but the impact they have on infants during this key window of development remains poorly understood. Through this study, we further characterize the effect antibiotics have on the gut microbiome of infants by looking at metagenomic sequencing data over time. MATERIALS AND METHODS: Stool samples were collected on infants from a large tertiary care neonatal intensive care unit. After DNA extraction, metagenomics libraries were generated and sequenced. Taxonomic and functional analyses were then performed. Further directed specimen sequencing for fungal species was also performed. RESULTS: A total of 51 stool samples from 25 infants were analyzed: seven infants were on antibiotics during at least one of their collection time points. Antibiotics given at birth altered the microbiome (PERMANOVA R2 = 0.044, p = .002) but later courses did not (R2 = 0.023, p = .114). Longitudinal samples collected while off antibiotics were more similar than those collected during a transition on or off antibiotics (mean Bray-Curtis distance 0.29 vs. 0.63, Wilcoxon p = .06). Functional analysis revealed four microbial pathways that were disrupted by antibiotics given at-birth (p < .1, folate synthesis, glycerolipid metabolism, fatty acid biosynthesis, and glycolysis). No functional changes associated with current antibiotic use were identified. In a limited sample set, we saw little evidence of fungal involvement in the overall infant microbiome. CONCLUSION: Through this study, we have further characterized the role antibiotics have in the development of the infant microbiome. Antibiotics given at birth were associated with alterations in the microbiome and had significant impact on the functional pathways involved in folate synthesis and multiple metabolic pathways. Later courses of antibiotics led to stochastic dysbiosis and a significant decrease in Escherichia coli. Further characterization of the infant mycobiome is still needed.


Asunto(s)
Microbioma Gastrointestinal , Antibacterianos , Disbiosis , Heces , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal
16.
Open Forum Infect Dis ; 8(6): ofaa551, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34095334

RESUMEN

BACKGROUND: The full spectrum of the disease phenotype and viral genotype of coronavirus disease 2019 (COVID-19) have yet to be thoroughly explored in children. Here, we analyze the relationships between viral genetic variants and clinical characteristics in children. METHODS: Whole-genome sequencing was performed on respiratory specimens collected for all SARS-CoV-2-positive children (n = 141) between March 13 and June 16, 2020. Viral genetic variations across the SARS-CoV-2 genome were identified and investigated to evaluate genomic correlates of disease severity. RESULTS: Higher viral load was detected in symptomatic patients (P = .0007) and in children <5 years old (P = .0004). Genomic analysis revealed a mean pairwise difference of 10.8 single nucleotide variants (SNVs), and the majority (55.4%) of SNVs led to an amino acid change in the viral proteins. The D614G mutation in the spike protein was present in 99.3% of the isolates. The calculated viral mutational rate of 22.2 substitutions/year contrasts the 13.5 substitutions/year observed in California isolates without the D614G mutation. Phylogenetic clade 20C was associated with severe cases of COVID-19 (odds ratio, 6.95; P = .0467). Epidemiological investigation revealed major representation of 3 of 5 major Nextstrain clades (20A, 20B, and 20C) consistent with multiple introductions of SARS-CoV-2 in Southern California. CONCLUSIONS: Genomic evaluation demonstrated greater than expected genetic diversity, presence of the D614G mutation, increased mutation rate, and evidence of multiple introductions of SARS-CoV-2 into Southern California. Our findings suggest a possible association of phylogenetic clade 20C with severe disease, but small sample size precludes a definitive conclusion. Our study warrants larger and multi-institutional genomic evaluation and has implications for infection control practices.

17.
Clin Infect Dis ; 50(7): e41-6, 2010 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-20178414

RESUMEN

BACKGROUND: The incidence of invasive Haemophilus influenzae infection decreased dramatically since the introduction of the H. influenzae serotype b (Hib) conjugate vaccine. H. influenzae invasive disease continues to occur and cause significant morbidity and mortality in children aged <5 years. We aimed to report the epidemiology and serotypes of invasive H. influenzae disease in children from Utah in the post-Hib vaccine era. METHODS: We identified all cases of invasive H. influenzae disease, defined as H. influenzae isolated from a sterile site, during the period 1998-2008 among children aged <18 years who were living in Utah. RESULTS: We identified 91 cases of invasive H. influenzae disease in children. Children aged <5 years accounted for 78 cases (86%). H. influenzae serotype a (Hia) was the most common serotype (22 cases), representing 28% of all cases of invasive disease among children aged <5 years. The majority (15 cases [93%]) of Hib disease cases occurred among children aged <5 years and accounted for 18% of all cases of H. influenzae invasive disease in this age group. The mean incidence of Hia disease increased from 0.8 cases per 100,000 child-years in 1998 to 2.6 cases per 100,000 child-years in 2008. The incidence of Hib disease among children aged <5 years remained steady at 0.5 cases per 100,000 child-years. Bacteremia accounted for 61% of all cases of invasive disease. One-half (13 of 26) of cases of H. influenzae meningitis were due to Hia. CONCLUSIONS: H. influenzae continues to cause invasive disease in Utah children. Hia is the primary cause of the overall increased incidence of invasive H. influenzae disease and leads to disease similar to Hib. Isolated cases of Hib disease demonstrate a continued reservoir. The success of the Hib conjugate vaccine may therefore be vulnerable to vaccine shortages and refusal of vaccination.


Asunto(s)
Cápsulas Bacterianas/administración & dosificación , Infecciones por Haemophilus/epidemiología , Vacunas contra Haemophilus/administración & dosificación , Haemophilus influenzae/aislamiento & purificación , Adolescente , Bacteriemia/epidemiología , Bacteriemia/microbiología , Cápsulas Bacterianas/genética , Niño , Preescolar , Femenino , Infecciones por Haemophilus/microbiología , Infecciones por Haemophilus/prevención & control , Haemophilus influenzae/clasificación , Haemophilus influenzae/genética , Humanos , Incidencia , Lactante , Masculino , Estudios Retrospectivos , Serotipificación , Utah/epidemiología
18.
Am J Infect Control ; 48(11): 1370-1374, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32512083

RESUMEN

BACKGROUND: Mobile phones are known to carry pathogenic bacteria and viruses on their surfaces, posing a risk to healthcare providers (HCPs) and hospital infection prevention efforts. We utilize an Ultraviolet-C (UV-C) device to provide an effective method for mobile phone disinfection and survey HCPs about infection risk. METHODS: Environmental swabs were used to culture HCPs' personal mobile phone surfaces. Four cultures were obtained per phone: before and after the UV-C device's 30-second disinfecting cycle, at the beginning and end of a 12-hour shift. Surveys were administered to participants pre- and poststudy. RESULTS: Total bacterial colony forming units were reduced by 90.5% (P = .006) after one UV-C disinfection cycle, and by 99.9% (P = .004) after 2 cycles. Total pathogenic bacterial colony forming units were decreased by 98.2% (P = .038) after one and >99.99% (P = .037) after 2 disinfection cycles. All survey respondents were willing to use the UV-C device daily to weekly, finding it convenient and beneficial. DISCUSSION: This novel UV-C disinfecting device is effective in reducing pathogenic bacteria on mobile phones. HCPs would frequently use a phone disinfecting device to reduce infection risk. CONCLUSIONS: In light of the ongoing coronavirus (COVID-19) pandemic, a standardized approach to phone disinfection may be valuable in preventing healthcare-associated infections.


Asunto(s)
Bacterias/efectos de la radiación , Betacoronavirus/efectos de la radiación , Teléfono Celular , Desinfección/instrumentación , Rayos Ultravioleta , Bacterias/patogenicidad , Betacoronavirus/patogenicidad , COVID-19 , Recuento de Colonia Microbiana , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Infección Hospitalaria/microbiología , Infección Hospitalaria/prevención & control , Transmisión de Enfermedad Infecciosa/prevención & control , Desinfección/métodos , Hospitales , Humanos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/virología , SARS-CoV-2 , Virulencia
19.
Cell Rep ; 33(3): 108275, 2020 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-33086075

RESUMEN

Neutralization of tumor necrosis factor (TNF) represents a widely used therapeutic strategy for autoimmune diseases including inflammatory bowel disease (IBD). However, the fact that many patients with IBD are non-responsive to anti-TNF therapies suggests the need for a better understanding of TNF signaling in IBD. Here, we show that co-deletion of TNF receptor 1 (TNFR1, Tnfrsf1a) in the Il10-/- spontaneous colitis model exacerbates disease, resulting in very-early-onset inflammation after weaning. The disease can be interrupted by treatment with antibiotics. The single deletion of TNFR1 induces subclinical colonic epithelial dysfunction and mucosal immune abnormalities, including accumulation of neutrophils and depletion of B cells. During the pre-disease period (before weaning), both Tnfr1-/- and Il10-/-Tnfr1-/- animals exhibit impaired expression of pro-inflammatory cytokines compared with wild-type and Il10-/- controls, respectively. Collectively, these results demonstrate the net anti-inflammatory functions of TNF/TNFR1 signaling through the regulation of colonic immune homeostasis in early life.


Asunto(s)
Colitis/genética , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Animales , Colitis/inmunología , Colitis/metabolismo , Colon/patología , Citocinas/metabolismo , Sulfato de Dextran/farmacología , Células Epiteliales/metabolismo , Femenino , Inflamación/patología , Enfermedades Inflamatorias del Intestino/patología , Interleucina-10/genética , Interleucina-10/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Receptores Tipo II del Factor de Necrosis Tumoral/metabolismo , Transducción de Señal/efectos de los fármacos , Inhibidores del Factor de Necrosis Tumoral/farmacología , Factor de Necrosis Tumoral alfa/metabolismo
20.
Emerg Infect Dis ; 15(1): 44-8, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19116048

RESUMEN

Bacterial pneumonia with empyema is a serious complication of influenza and commonly resulted in death during the 1918 influenza pandemic. We hypothesize that deaths caused by parapneumonic empyema are increasing in Utah once again despite advances in critical care and the availability of antimicrobial drugs and new vaccines. In this study, we analyzed the historical relationship between deaths caused by empyema and influenza pandemics by using 100 years of data from Utah. Deaths caused by empyema have indeed increased from 2000-2004 when compared with the historic low death rates of 1950-1975. Vaccine strategies and antimicrobial drug stockpiling to control empyema will be important as we prepare for the next influenza pandemic.


Asunto(s)
Empiema Pleural/historia , Empiema Pleural/mortalidad , Gripe Humana/historia , Neumonía Bacteriana/historia , Neumonía Neumocócica/historia , Adolescente , Adulto , Niño , Brotes de Enfermedades/historia , Brotes de Enfermedades/estadística & datos numéricos , Empiema Pleural/epidemiología , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Lactante , Gripe Humana/complicaciones , Gripe Humana/epidemiología , Gripe Humana/mortalidad , Neumonía Bacteriana/mortalidad , Neumonía Neumocócica/mortalidad , Utah/epidemiología
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