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Choanephora infundibulifera is a member of the Mucorales order of fungi. The species is associated with plants as a saprophyte or parasite and may be responsible for spoilage or disease but is an uncommon cause of human infection. We describe C. infundibulifera rhinosinusitis in a young man with leukemia in Tennessee, USA.
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Sinusite , Humanos , Masculino , Tennessee , Sinusite/microbiologia , Sinusite/diagnóstico , Sinusite/parasitologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Mucormicose/diagnóstico , Mucormicose/microbiologia , Mucormicose/tratamento farmacológico , Mucorales/isolamento & purificação , Mucorales/classificação , Rinite/microbiologia , Rinite/diagnóstico , Adulto , Antifúngicos/uso terapêutico , RinossinusiteRESUMO
Although mucormycosis is an important cause of morbidity and mortality in children with cancer, our understanding of the typical characteristics of these infections is incomplete. We reviewed all cases of mucormycosis diagnosed at a single pediatric cancer center over 5 decades to identify the clinical features of mucormycosis in pediatric oncology patients and to identify risk factors for mortality. There were 44 cases of mucormycosis diagnosed between 1970-2019. Most patients (89%) had hematological malignancies and a history of prolonged and severe neutropenia (91%). In this series, hyperglycemia and exposure to corticosteroids were common. Pulmonary (36%) and disseminated infections (32%) were most common; rhino-orbital-cerebral infections were relatively infrequent (11%). Rhizopus spp. was the most common etiological agent (40%) followed by Mucor spp. (31%), and Cunninghamella spp. (19%). Overall mortality was 44% and 51% and attributable mortality was 39% and 41% at the end of antifungal therapy and end of follow up, respectively. Attributable mortality fell to 18% in 2010-2019, from 58-60% in previous decades; adjunctive surgery was associated with decreased mortality. Mortality remains unacceptably high despite aggressive antifungal therapy and adjunctive surgery, suggesting novel therapeutic strategies are needed.
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Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Mucormicose , Neutropenia , Humanos , Criança , Mucormicose/diagnóstico , Antifúngicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos de Coortes , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Neutropenia/complicaçõesRESUMO
BACKGROUND: Respiratory viral infections are common among pediatric transplant patients, with human rhinovirus (HRV) being the most frequent. In pediatric patients undergoing hemopoietic cell transplant (HCT), infection with HRV has been associated with progression to lower respiratory tract infection (LRTI) and adverse outcomes. We describe the clinical presentation and outcomes of HRV infection in children undergoing HCT. METHODS: Single-center retrospective study. HCT recipients who were positive for HRV/EV (HRV+) or negative for any respiratory virus (VN) by BioFire® FilmArray® panel between October 2014 and December 2017, were included. Primary outcomes were progression to LRTI, ICU admission, all-cause mortality at 3 and 6 months, and respiratory event-related mortality at 6 months. RESULTS: 227 patients (160 allogeneic HCT) were included. Of all patients, 108/227 (47.6%) were HRV+. From all HRV+, 95/108 (88%) were symptomatic and 68/107 (63.6%) of the diagnosis were made pretransplant. The median age of HRV+ was significantly lower than VN patients (5 vs 10 years). Cough and rhinorrhea were more frequently observed in HRV+ (53.7 and 60% vs 19.8 and 22.8%, respectively). No differences were found between both groups pretransplant and overall in rates progression to LRTI, ICU admission, mechanical ventilation, all-cause within 3 and 6 months, and mortality related with respiratory failure. No significant association was found between the severity of respiratory disease and the type of conditioning, type of transplant, or absolute lymphocyte count. CONCLUSIONS: HRV infection is frequently detected in HCT recipients but is not associated with severity of respiratory disease, need for intensive care unit or mortality, including those diagnosed before transplant, suggesting that delaying HCT in this scenario may not be needed. Multicenter larger studies are required to confirm these findings.
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Infecções por Enterovirus , Enterovirus , Infecções por Picornaviridae , Infecções Respiratórias , Criança , Humanos , Transplante de Células/efeitos adversos , Estudos Retrospectivos , Rhinovirus , Pré-Escolar , LactenteRESUMO
BACKGROUND: The role of SARS-CoV-2 viral load in predicting contagiousness, disease severity, transmissibility, and clinical decision-making continues to be an area of great interest. However, most studies have been in adults and have evaluated SARS-CoV-2 loads using cycle thresholds (Ct) values, which are not standardized preventing consistent interpretation critical to understanding clinical impact and utility. Here, a quantitative SARS-CoV-2 reverse-transcription digital PCR (RT-dPCR) assay normalized to WHO International Units was applied to children at risk of severe disease diagnosed with COVID-19 at St. Jude Children's Research Hospital between March 28, 2020, and January 31, 2022. METHODS: Demographic and clinical information from children, adolescents, and young adults treated at St. Jude Children's Research Hospital were abstracted from medical records. Respiratory samples underwent SARS-CoV-2 RNA quantitation by RT-dPCR targeting N1 and N2 genes, with sequencing to determine the genetic lineage of infecting virus. RESULTS: Four hundred and sixty-two patients aged 0-24 years (median 11 years old) were included during the study period. Most patients were infected by the omicron variant (43.72%), followed by ancestral strain (22.29%), delta (13.20%), and alpha (2.16%). Viral load at presentation ranged from 2.49 to 9.14 log10 IU/mL, and higher viral RNA loads were associated with symptoms (OR 1.32; CI 95% 1.16-1.49) and respiratory disease (OR 1.23; CI 95% 1.07-1.41). Viral load did not differ by SARS-CoV-2 variant, vaccination status, age, or baseline diagnosis. CONCLUSIONS: SARS-CoV-2 RNA loads predict the presence of symptomatic and respiratory diseases. The use of standardized, quantitative methods is feasible, allows for replication, and comparisons across institutions, and has the potential to facilitate consensus quantitative thresholds for risk stratification and treatment.
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COVID-19 , SARS-CoV-2 , Criança , Adulto Jovem , Humanos , Adolescente , SARS-CoV-2/genética , RNA Viral/genética , COVID-19/diagnóstico , Reação em Cadeia da Polimerase , Carga Viral , Teste para COVID-19RESUMO
The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the overarching species and that of the molecular sibling, often cryptic species. Because the use of different names for the same species will be unavoidable for many years to come, an open access online database of the names of all medically important fungi, with proper nomenclatural designation and synonymy, is essential. We further recommend that while taxonomic discovery continues, the adaptation of new name changes by clinical laboratories and clinicians be reviewed routinely by a standing committee for validation and stability over time, with reference to an open access database, wherein reasons for changes are listed in a transparent way.
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Fungos , Humanos , Filogenia , Bases de Dados Factuais , Fungos/genéticaRESUMO
From 8 December 2021 to 26 January 2023, tixagevimab-cilgavimab (T-C) was authorized for pre-exposure prophylaxis of COVID-19. During this period, we used a multidisciplinary team to communicate, screen, approach, and administer T-C to eligible patients. Twenty-seven patients were eligible. Of these, 24 (88.9%) received at least one dose of T-C and three patients received two doses. Majority of patients were White, non-Hispanic, and women. Only two patients had COVID-19 prior to receiving T-C. Seventeen (70.8%) had received two or more doses of SARS-CoV-2 vaccine. No serious adverse events were noted. Seven patients developed SARS-CoV-2 infection within 180 days of receiving T-C (median 102 days; range 28-135), and only one patient developed severe COVID-19 requiring intensive mechanical ventilation in the intensive care unit.
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BACKGROUND: Despite preventive measures, infections continue to pose significant risks to pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The gut microbiota has been linked to clinical outcomes following adult allo-HCT. This study evaluated whether similar disruptions or differing microbiota patterns were associated with infection risk in pediatric allo-HCT. METHODS: In a prospective observational study, fecal samples were obtained from 74 children before conditioning and upon neutrophil recovery. Microbiome signatures identified through sequencing were examined for their associations with infections or acute graft-versus-host disease (aGVHD) in the first-year post-HCT using Cox proportional hazards analysis. RESULTS: Microbiome disruption in adults, did not predict infection risk in pediatric allo-HCT. Unique microbiota signatures were associated with different infections or aGVHD. A ratio of strict and facultative anaerobes (eg, Lachnoclostridium, Parabacteroides) prior to conditioning predicted bacteremia risk (Cox hazard ratio [HR], 3.89). A distinct ratio of oral (eg, Rothia, Veillonella) to intestinal anaerobes (eg, Anaerobutyricum, Romboutsia) at neutrophil recovery predicted likelihood of bacterial infections (Cox HR, 1.81) and viral enterocolitis (Cox HR, 1.96). CONCLUSIONS: Interactions between medical interventions, pediatric hosts, and microbial communities contribute to microbiota signatures that predict infections. Further multicenter study is necessary to validate the generalizability of these ratios as biomarkers.
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Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Bactérias/genética , Fezes/microbiologiaRESUMO
Immunocompromised patients can have life-threatening adenoviral infection. Viral load in blood and stool is commonly used to guide antiviral therapy. We developed and evaluated a digital polymerase chain reaction assay to quantify human adenovirus in the respiratory tract and showed that higher peak load correlates with disseminated infection, mechanical ventilation, and death.
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We describe a cluster of 6 pediatric hematopoietic cell transplant recipients with Lactobacillus bacteremia attributed to probiotic use. Lactobacillus isolates cultured from probiotics and patients' blood were proven to be related using whole-genome sequencing. Clinical studies are needed to evaluate the safety of probiotic use in immunocompromised patients.
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Bacteriemia , Transplante de Células-Tronco Hematopoéticas , Probióticos , Humanos , Criança , Lactobacillus/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Bacteriemia/prevenção & controle , Hospedeiro Imunocomprometido , Probióticos/uso terapêuticoRESUMO
BACKGROUND: The incidence of Clostridioides difficile infection (CDI) has been rising among hospitalized children, with poor understanding of genomic variability of C. difficile isolates in this population. METHODS: This was a retrospective cohort study of CDI in inpatient and outpatient pediatric oncology and cell transplant patients (POTPs) in 2016 and 2017. CDI cases were identified by positive C. difficile toxin polymerase chain reaction tests. Retrieved residual stool specimens were cultured anaerobically and toxin-producing C. difficile isolates underwent whole genome sequencing (WGS) followed by core genome multilocus sequence typing. Plausible time and location epidemiologic links among the closely related strains were evaluated to identify potential transmission events. RESULTS: Among 226 CDI episodes in 157 patients, 202 stool samples were cultured and had positive cytotoxicity tests. Sequencing identified 33 different strain types in 162 (80%) isolates. Thirty-nine (28%) patients had multiple episodes of CDI, and 31 clusters of related isolates were identified, 15 (47%) of which involved exclusively multiple specimens from the same patient. For the 16 clusters involving multiple patients, epidemiologic investigation revealed only 2 (12.5%) clusters with potential transmission events. CONCLUSIONS: WGS identified a highly diverse group of C. difficile isolates among POTPs with CDI. Although WGS identified clusters of closely related isolates in multiple patients, epidemiologic investigation of shared inpatient exposures identified potential transmission in only 2 clusters. Clostridioides difficile transmission was uncommon in this population. More than 70% of new CDI reinfections in POTPs are actually recurrences caused by a previous CDI strain.
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Clostridioides difficile , Infecções por Clostridium , Neoplasias , Criança , Humanos , Clostridioides difficile/genética , Clostridioides/genética , Epidemiologia Molecular , Estudos Retrospectivos , Sequenciamento Completo do Genoma , Infecções por Clostridium/epidemiologiaRESUMO
Background: Case investigations and contact tracing are essential disease control measures used by health departments. Early in the pandemic, they were seen as a key strategy to stop COVID-19 spread. The CDC urged rapid action to scale up and train a large workforce and collaborate across public and private agencies to halt COVID-19 transmission. Methods: We developed a program for case investigation and contact tracing that followed CDC and local health guidelines, compliant with the Occupational Safety and Health Administration (OSHA) regulations and tailored to the needs and resources of our institution. Program staff were trained and assessed for competency before joining the program. Results: From March 2020 to May 2021, we performed 838 COVID-19 case investigations, which led to 136 contacts. Most employees reported a known SARS-CoV-2 exposure from the community (n = 435) or household (n = 343). Only seven (5.1%) employees were determined as more likely than not to have SARS-CoV-2 infection related to workplace exposure, and when so, lapses in following the masking recommendations were identified. Between June 2021-February 2022, our program adjusted to the demand of the different waves, particularly omicron, by significantly reducing the amount of data collected. No transmission from employees to patients or caregivers was observed during this period. Conclusion: Prompt implementation of case investigation and contact tracing is possible, and it effectively reduces workplace exposures. This approach can be adapted to suit the specific needs and requirements of various healthcare settings, particularly those serving the most vulnerable patient populations.
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COVID-19 , Neoplasias , Estados Unidos , Humanos , Criança , COVID-19/epidemiologia , COVID-19/prevenção & controle , Cuidadores , Institutos de Câncer , Busca de Comunicante , SARS-CoV-2 , Recursos Humanos , Hospitais PediátricosRESUMO
Although numerous studies have evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using cycle threshold (Ct) values as a surrogate of viral ribonucleic acid (RNA) load, few studies have used standardized, quantitative methods. We validated a quantitative SARS-CoV-2 digital polymerase chain reaction assay normalized to World Health Organization International Units and correlated viral RNA load with symptoms and disease severity.
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Human parvovirus B19 causes life-threatening anemia due to transient red cell aplasia (TRCA) in individuals with sickle cell disease (SCD). Children with SCD experiencing profound anemia during TRCA often require red blood cell transfusions and hospitalization. The prevalence of vitamin deficiencies in SCD is high and deficiencies are associated with respiratory and pain symptoms, but the effects of vitamins on acute infection with parvovirus B19 remain unclear. We performed a clinical study in which 20 SCD patients hospitalized with parvovirus B19 infections (Day 0) were monitored over a 120-day time course to query relationships between vitamins A and D and clinical outcomes. There were significant negative correlations between Day 0 vitamin levels and disease consequences (e.g., red blood cell transfusion requirements, inflammatory cytokines). There were significant positive correlations (i) between Day 0 vitamins and peak virus-specific antibodies in nasal wash, and (ii) between Day 0 virus-specific serum plus nasal wash antibodies and absolute reticulocyte counts. There was a significant negative correlation between Day 0 virus-specific serum antibodies and virus loads. To explain the results, we propose circular and complex mechanisms. Low baseline vitamin levels may weaken virus-specific immune responses to permit virus amplification and reticulocyte loss; consequent damage may further reduce vitamin levels and virus-specific immunity. While the complex benefits of vitamins are not fully understood, we propose that maintenance of replete vitamin A and D levels in children with SCD will serve as prophylaxis against parvovirus B19-induced TRCA complications.
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Anemia Falciforme , Infecções por Parvoviridae , Parvovirus B19 Humano , Anemia Falciforme/complicações , Anemia Falciforme/terapia , Anticorpos Antivirais , Criança , Humanos , Infecções por Parvoviridae/complicações , Infecções por Parvoviridae/epidemiologia , Vitamina A , VitaminasRESUMO
BACKGROUND: COVID-19 has caused over 305 million infections and nearly 5.5 million deaths globally. With complete eradication unlikely, organizations will need to evaluate their risk and the benefits of mitigation strategies, including the effects of regular asymptomatic testing. We developed a web application and R package that provides estimates and visualizations to aid the assessment of organizational infection risk and testing benefits to facilitate decision-making, which combines internal and community information with malleable assumptions. RESULTS: Our web application, covidscreen, presents estimated values of risk metrics in an intuitive graphical format. It shows the current expected number of active, primarily community-acquired infections among employees in an organization. It calculates and explains the absolute and relative risk reduction of an intervention, relative to the baseline scenario, and shows the value of testing vaccinated and unvaccinated employees. In addition, the web interface allows users to profile risk over a chosen range of input values. The performance and output are illustrated using simulations and a real-world example from the employee testing program of a pediatric oncology specialty hospital. CONCLUSIONS: As the COVID-19 pandemic continues to evolve, covidscreen can assist organizations in making informed decisions about whether to incorporate covid test based screening as part of their on-campus risk-mitigation strategy. The web application, R package, and source code are freely available online (see "Availability of data and materials").
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COVID-19 , Aplicativos Móveis , COVID-19/diagnóstico , COVID-19/prevenção & controle , Teste para COVID-19 , Criança , Humanos , Programas de Rastreamento , Pandemias/prevenção & controleRESUMO
Novel human astroviruses (HAstVs) have recently been implicated as rare causes of fatal encephalitis in immunocompromised patients, for which there is no proven treatment. We report 2 cases from our institution in which HAstV-VA1 was detected in the cerebrospinal fluid by metagenomic next-generation sequencing after the initial evaluation revealed no etiology.
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Infecções por Astroviridae , Encefalite , Mamastrovirus , Neoplasias , Infecções por Astroviridae/diagnóstico , Criança , Fezes , Humanos , Hospedeiro Imunocomprometido , Mamastrovirus/genética , FilogeniaRESUMO
COVID-19 remains a challenge worldwide, and testing of asymptomatic individuals remains critical to pandemic control measures. Starting March 2020, a total of 7497 hospital employees were tested at least weekly for SARS CoV-2; the cumulative incidence of asymptomatic infections was 5.64%. Consistently over a 14-month period half of COVID-19 infections (414 of 820, total) were detected through the asymptomatic screening program, a third of whom never developed any symptoms during follow-up. Prompt detection and isolation of these cases substantially reduced the risk of potential workplace and outside of workplace transmission. COVID-19 vaccinations of the workforce were initiated in December 2020. Twenty-one individuals tested positive after being fully vaccinated (3.9 per 1000 vaccinated). Most (61.9%) remained asymptomatic and in majority (75%) the virus could not be sequenced due to low template RNA levels in swab samples. Further routine testing of vaccinated asymptomatic employees was stopped and will be redeployed if needed; routine testing for those not vaccinated continues. Asymptomatic SARS-CoV-2 testing, as a part of enhanced screening, monitors local dynamics of the COVID-19 pandemic and can provide valuable data to assess the ongoing impact of COVID-19 vaccination and SARS-CoV-2 variants, inform risk mitigation, and guide adaptive, operational planning including titration of screening strategies over time, based on infection risk modifiers such as vaccination.
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COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Teste para COVID-19 , Vacinas contra COVID-19 , Humanos , Pandemias/prevenção & controle , SARS-CoV-2 , Recursos HumanosRESUMO
OBJECTIVE: The objective of this study is to assess the utility of a nucleic acid amplification test-based approach to shorten isolation of healthcare workers (HCWs) with COVID-19 in the setting of the highly transmissible omicron variant. METHODS: Between December 24, 2021, and January 5, 2022, HCWs who tested positive for SARS-CoV-2 were retested with PCR at least 5 days since onset of symptoms. RESULTS: Forty-six sequential fully COVID-19 vaccinated HCWs who had tested positive for SARS-CoV-2 underwent follow-up testing. All the samples were confirmed as omicron variants and only four (8.7%) were negative in the follow-up test performed at a median of 6 (range 5-12) since onset of symptoms. CONCLUSIONS: Implementation of a test-based strategy is logistically challenging, increases costs, and did not lead to shorter isolation in our institution.
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COVID-19 , Pessoal de Saúde , Humanos , Técnicas de Amplificação de Ácido Nucleico , Retorno ao Trabalho , SARS-CoV-2/genéticaRESUMO
A quantitative PCR method was developed for the detection of Clostridioides difficile Chaperonin-60 gene. The method had a specificity for C. difficile strains of clinical and epidemiological importance and allowed for quantification of C. difficile cells and spores.