Detection of invasive Bartonella infections with next-generation sequencing of microbial cell-free DNA.

We report 9 patients with invasive Bartonella infections, including 5 with endocarditis, who were diagnosed with microbial cell-free DNA next-generation sequencing and Bartonella serology studies. Diagnosis with plasma mcfDNA NGS enabled a faster clinical and laboratory diagnosis in 8 patients. Prompt diagnosis impacted antibiotic management in all 9 patients.

Host and environmental factors influencing respiratory secretion of pro-wheezing biomarkers in preterm children.

Cytokines are actively secreted by the respiratory mucosa of preterm children and participate in the pathogenesis of wheezing. This study aimed to identify the factors that could potentially influence respiratory secretion of cytokines in these children. A nasopharyngeal aspirate (NPA) was collected from 77 preterm children 1 yr after birth. NPAs from 14 healthy, 1-yr-old term children were collected in parallel. 27 cytokines were measured in the NPAs using a multiplex assay. Multivariate stepwise regression analysis with Bonferroni correction evidenced that the variable [daycare attendance] was associated with higher levels of [monocyte chemoattractant protein-1 (MCP-1), IL-6, vascular endothelial growth factor (VEGF), IL-1ß, IL-10, tumor necrosis factor (TNF)-α]; [male sex] with higher levels of (MCP-1, VEGF, and IL-1ß); [smokers at home] was associated with higher levels of MCP-1 (p < 0.0013). In turn, [prophylaxis with palivizumab] was associated with lower levels of (IL-6, IL-7) (p < 0.0013). All these mediators participate in the pathogenesis of asthma and recurrent wheezing. Preterm children secreted higher levels of chemokines (interferon-gamma inducible protein-10, macrophage inflammatory protein-1α, Eotaxin, MCP-1), growth factors (platelet-derived growth factor-bb, VEGF, fibroblast growth factor-basic, granulocyte macrophage colony-stimulating factor), Th1 (IL12, interferon-γ), Th2 (IL-9, IL-13), Th17 (IL-6, IL-17) cytokines, and immunomodulatory mediators (IL1RA and granulocyte colony-stimulating factor) than term children. In conclusion, we have identified for the first time a group of individual and environmental factors influencing respiratory secretion of cytokines in preterm children at the long term after birth. To know these factors could help to prevent the instauration of conditions linked to the appearance of chronic respiratory diseases such as wheezing or asthma.

Reviewing a Decade of Outpatient Tropical Medicine in Houston, Texas.

Tropical diseases cause significant morbidity among the world's poorest populations. Although more common in low- and middle-income countries, tropical diseases are also found among underserved populations living in high-income countries such as the United States. The National School of Tropical Medicine at Baylor College of Medicine and the Harris Health System founded a tropical medicine clinic-the Harris Health Tropical Medicine Clinic (HHTMC)-in Houston in 2011 in response to tropical disease-related morbidity in Texas. We conducted a retrospective chart review of a sample of patients older than 18 years of age who were referred to the HHTMC between October 2011 and January 2020. Of the 523 patients reviewed, 185 (35.4%) had mycobacterial infections, 184 (35.2%) had parasitic infections, 38 (7.3%) had fungal infections, 16 (3.1%) had eosinophilia without a confirmed clinical diagnosis, 28 (5.4%) had bacterial infections, and 13 (2.5%) had viral infections. The most common infections overall were extrapulmonary and latent tuberculosis (n = 169), neurocysticercosis (n = 78), strongyloidiasis (n = 28), Chagas disease (n = 25), and schistosomiasis (n = 12). The epidemiology of tropical diseases in the United States is understudied at national and regional levels. This 10-year retrospective study contributes to bridging this knowledge gap by detailing the frequencies of tropical disease diagnoses made at the HHTMC in Houston, TX. These data highlight areas for advancement in the field of tropical medicine within the United States, such as improving front-line health-care provider education; establishing tropical medicine clinics in areas of high prevalence such as the Gulf Coast, Appalachia, and urban areas; and developing comprehensive, systematic national tropical disease screening programs and patient registries.

External validation of the HCM Risk-Kids model for predicting sudden cardiac death in childhood hypertrophic cardiomyopathy.

AIMS: Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM). The newly developed HCM Risk-Kids model provides clinicians with individualized estimates of risk. The aim of this study was to externally validate the model in a large independent, multi-centre patient cohort. METHODS AND RESULTS: A retrospective, longitudinal cohort of 421 patients diagnosed with HCM aged 1-16 years independent of the HCM Risk-Kids development and internal validation cohort was studied. Data on HCM Risk-Kids predictor variables (unexplained syncope, non-sustained ventricular tachycardia, maximal left ventricular wall thickness, left atrial diameter, and left ventricular outflow tract gradient) were collected from the time of baseline clinical evaluation. The performance of the HCM Risk-Kids model in predicting risk at 5 years was assessed. Twenty-three patients (5.4%) met the SCD end-point within 5 years, with an overall incidence rate of 2.03 per 100 patient-years [95% confidence interval (CI) 1.48-2.78]. Model validation showed a Harrell's C-index of 0.745 (95% CI 0.52-0.97) and Uno's C-index 0.714 (95% 0.58-0.85) with a calibration slope of 1.15 (95% 0.51-1.80). A 5-year predicted risk threshold of ≥6% identified 17 (73.9%) SCD events with a corresponding C-statistic of 0.702 (95% CI 0.60-0.81). CONCLUSIONS: This study reports the first external validation of the HCM Risk-Kids model in a large and geographically diverse patient population. A 5-year predicted risk of ≥6% identified over 70% of events, confirming that HCM Risk-Kids provides a method for individualized risk predictions and shared decision-making in children with HCM.

Erratum to: Clinical Features and Outcomes of Community-Acquired Pneumonia Caused by Haemophilus influenzae.

[This corrects the article DOI: 10.1093/ofid/ofaa622.].

Clinical Features and Outcomes of Community-Acquired Pneumonia Caused by Haemophilus Influenza.

BACKGROUND: Long regarded as the second most common cause of community-acquired pneumonia (CAP), Haemophilus influenzae has recently been identified with almost equal frequency as pneumococcus in patients hospitalized for CAP. The literature lacks a detailed description of the presentation, clinical features, laboratory and radiologic findings, and outcomes in Haemophilus pneumonia. METHODS: During 2 prospective studies of patients hospitalized for CAP, we identified 33 patients with Haemophilus pneumonia. In order to provide context, we compared clinical findings in these patients with findings in 36 patients with pneumococcal pneumonia identified during the same period. We included and analyzed separately data from patients with viral coinfection. Patients with coinfection by other bacteria were excluded. RESULTS: Haemophilus pneumonia occurred in older adults who had underlying chronic lung disease, cardiac conditions, and alcohol use disorder, the same population at risk for pneumococcal pneumonia. However, in contrast to pneumococcal pneumonia, patients with Haemophilus pneumonia had less severe infection as shown by absence of septic shock on admission, less confusion, fewer cases of leukopenia or extreme leukocytosis, and no deaths at 30 days. Viral coinfection greatly increased the severity of Haemophilus, but not pneumococcal pneumonia. CONCLUSIONS: We present the first thorough description of Haemophilus pneumonia, show that it is less severe than pneumococcal pneumonia, and document that viral coinfection greatly increases its severity. These distinctions are lost when the label CAP is liberally applied to all patients who come to the hospital from the community for pneumonia.

Characteristics of Rickettsia typhi Infections Detected with Next-Generation Sequencing of Microbial Cell-Free Deoxyribonucleic Acid in a Tertiary Care Hospital.

We present 10 patients with Rickettsia typhi infection in whom next-generation sequencing of microbial cell-free deoxyribonucleic acid (mcfDNA) was used as a diagnostic tool. Rickettsia typhi mcfDNA was detected in all cases and was more rapid and specific than rickettsial serology. Rickettsia typhi mcfDNA impacted antibiotic management in 50% of patients.

Successful Detection of Unrecognized Rickettsia typhi in Pregnancy Using Cell-Free Next-Generation Sequencing.

Flea-borne (murine) typhus is caused by Rickettsia typhi. Infection in pregnant women can lead to adverse outcomes when diagnosis and treatment is delayed. We describe how next-generation sequencing (NGS) using the Karius® test was used to rapidly diagnose murine typhus in two pregnant women admitted to a large tertiary care center in Houston, Texas, when all initial testing was nondiagnostic.

Screening for subtelomeric chromosome alteration in a consecutive series of newborns with congenital defects.

It is generally accepted that 2.5% of the patients with unexplained mental retardation and dysmorphic features have a chromosome alteration affecting the subtelomeric regions. The frequency of such alterations whether in the general population or in newborns with congenital defects, however, remains unknown. Here, we present an analysis of the subtelomeric regions in a consecutive series of 71 newborn babies with congenital defects, who displayed a normal high resolution G-band karyotype (550-850 bands). After excluding the alterations that could be considered to be polymorphisms, a total of seven subtelomeric anomalies were observed with a frequency of 9.86% (3.96-20.31). We conclude that fluorescence in-situ hybridization screening for subtelomeric alterations is relevant for infants with congenital defects detectable at birth, particularly in those newborn babies with congenital defects and a normal high resolution G-band karyotype.

[Atrioventricular canal defect, single atrium and tricuspid atresia as part of a case of Ellis-Van Creveld syndrome]. / Defecto del canal auriculoventricular, aurícula única y atresia tricuspídea como parte de un caso de síndrome de Ellis-Van Creveld.

Ellis-Van Creveld Syndrome or chondrectodermal dysplasia is produced by an autosomal recessive inheritance secondary to mutation in the short arm of chromosome 4. The syndrome affects multiple organs. It is described as a clinical tetrad that involves chondrodysplasia, ectodermal dysplasia, polydactyly and congenital heart defects. It is only known from reports and case series. We present a three months old male, without relevant family history, who presented chondrodysplasia, upper lip merged to palate, bilateral sinpolydactyly in the hands, developmental dysplasia of the hip, narrow chest with short ribs, and heart defects. This case is the first report of EVC in Peruvian literature.

Five-year antibody persistence and safety following a booster dose of combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine.

BACKGROUND: Booster vaccination with the combined Haemophilus influenza type b-Neisseria meningitides serogroup C-tetanus toxoid vaccine (Hib-MenC-TT) has been reported to induce different MenC antibody responses depending on the priming vaccines, with a possible impact on long-term protection. Here, the five-year persistence of immune responses induced by a booster dose of Hib-MenC-TT was evaluated in toddlers primed with either Hib-MenC-TT or MenC-TT. METHODS: This is the follow-up of a phase III, open, randomized study, in which a Hib-MenC-TT booster dose was given at 13.14 months of age to toddlers primed with either 3 doses of Hib-MenC-TT or 2 doses of MenC-TT in infancy. Children in the control group had received 3 primary doses and a booster dose of MenC-CRM197. Functional antibodies against MenC were measured by a serum bactericidal assay with rabbit complement (rSBA-MenC) and antibodies against Hib polyribosylribitol phosphate by enzyme-linked immunosorbent assay. Serious adverse events considered by the investigator to be possibly related to vaccination were to be reported throughout the study. RESULTS: At 66 months postbooster, rSBA-MenC titers ≥8 were retained by 82.6% of children primed with Hib-MenC-TT, 94.1% of children primed with MenC-TT, and 60.9% of children in the control group. All children who received the Hib-MenC-TT booster dose retained anti- polyribosylribitol phosphate concentrations ≥0.15 µg/mL. No serious adverse events considered possibly related to vaccination were reported. CONCLUSIONS: There is evidence of good antibody persistence against MenC and Hib for more than five years postbooster vaccination with Hib-MenC TT in toddlers primed with Hib-MenC-TT or MenC-TT.

Defecto del canal auriculoventricular, aurícula única y atresia tricuspídea como parte de un caso de síndrome de Ellis-Van Creveld / Atrioventricular canal defect, single atrium and tricuspid atresia as part of a case of Ellis-Van Creveld syndrome

El síndrome de Ellis-Van Creveld (SEVC) o displasia condroectodérmica se debe a una mutación de transmisión autosómica recesiva en el brazo corto del cromosoma 4 y afecta múltiples órganos. Descrito como una tétrada clásica de condrodisplasia, displasia ectodérmica, polidactilia y defectos cardíacos congénitos, sólo se conoce a partir de informes y series de casos. Se describe el caso de un varón de 3 meses, sin antecedentes familiares de importancia, que presentó un cuadro de condrodisplasia, labio superior fusionado al paladar, simpolidactilia posaxial bilateral en las manos, displasia del desarrollo de las caderas, tórax estrecho con costillas cortas y compromiso cardíaco. El presente caso sería la primera comunicación del SEVC en el Perú.

Ellis-Van Creveld Syndrome or chondrectodermal dysplasia is produced by an autosomal recessive inheritance secondary to mutation in the short arm of chromosome 4. The syndrome affects multiple organs. It is described as a clinical tetrad that involves chondrodysplasia, ectodermal dysplasia, polydactyly and congenital heart defects. It is only known from reports and case series. We present a three months old male, without relevant family history, who presented chondrodysplasia, upper lip merged to palate, bilateral sinpolydactyly in the hands, developmental dysplasia of the hip, narrow chest with short ribs, and heart defects. This case is the first report of EVC in Peruvian literature.

Análisis ultraestructural de la interacción de xanthomonas axonopodis pv. phaseoli con genotipos resistentes, moderadamente resistentes y susceptibles de phaseolus vulgaris l / Ultrastructural analysis of the interactions between xanthomonas axonopodis pv. phaseoli and resistant, moderately resistan and susceptible genotypes of phaseolus vulgaris l

Observaciones al microscopio electrónico de transmisión de secciones transversales de hojas de caraota (Phaseolus vulgaris L) inoculadas con Xanthomonas axonopodis pv. phaseoli (Xapvph) a los 17 y 27 días después de la siembra, permitieron visualizar los cambios ocurridos a nivel celular en la epidermis, mesófilo y tejido vascular en genotipos resistentes, moderadamente resistentes y susceptibles. Las muestras fueron tomadas y procesadas a los 14 y 21 días después de la inoculación. En el genotipo resistente se observó el fenómeno de encapsulación; en el genotipo moderadamente resisrente se observaron pocas bacterias en los espacios intercelulares y formación de vesículas entre el plasmalemma y la pared celular. En el genotipo susceptible, hubo mayor número de bacterias en los espacios intercelulares, condensación del citoplasma, desintegración de organelas, rompimiento de la lámina media y penetración en el tejido vascular (vasos del metaxilema) de masas de células bacteriales. Con este resultado se comprobó que en estadios tardíos la bacteria Xapvph entra al tejido vascular