Development and Evaluation of an NTM-IGRA to Guide Pediatric Lymphadenitis Diagnosis.

BACKGROUND: Diagnosis of nontuberculous mycobacteria (NTM) infections remains a challenge. In this study, we describe the evaluation of an immunological NTM-interferon (IFN)-γ release assay (IGRA) that we developed using glycopeptidolipids (GPLs) as NTM-specific antigens. METHODS: We tested the NTM-IGRA in 99 samples from pediatric patients. Seventy-five were patients with lymphadenitis: 25 were NTM confirmed, 45 were of unknown etiology but compatible with mycobacterial infection and 5 had lymphadenitis caused by an etiologic agent other than NTM. The remaining 24 samples were from control individuals without lymphadenitis (latently infected with M. tuberculosis , uninfected controls and active tuberculosis patients). Peripheral blood mononuclear cells were stimulated overnight with GPLs. Detection of IFN-γ producing cells was evaluated by enzyme-linked immunospot assay. RESULTS: NTM culture-confirmed lymphadenitis patient samples had a significantly higher response to GPLs than the patients with lymphadenitis of unknown etiology but compatible with mycobacterial infection ( P < 0.001) and lymphadenitis not caused by NTM ( P < 0.01). We analyzed the response against GPLs in samples from unknown etiology lymphadenitis but compatible with mycobacterial infection cases according to the tuberculin skin test (TST) response, and although not statistically significant, those with a TST ≥5 mm had a higher response to GPLs when compared with the TST <5 mm group. CONCLUSIONS: Stimulation with GPLs yielded promising results in detecting NTM infection in pediatric patients with lymphadenitis. Our results indicate that the test could be useful to guide the diagnosis of pediatric lymphadenitis. This new NTM-IGRA could improve the clinical handling of NTM-infected patients and avoid unnecessary misdiagnosis and treatments.

Challenges in the application of non-servocontrolled therapeutic hypothermia during neonatal transport in Catalonia.

INTRODUCTION: Therapeutic hypothermia (TH) improves survival and neurological prognosis in hypoxic-ischemic encephalopathic (HIE) babies, being better the sooner TH is implemented. HIE babies are born more frequently in a non-cooling centre and need to be referred. METHODS: Prospective-observational study (April 18 2018 - November 19 2019). Newborns (≥34 weeks of gestational age (GA) and >1800 g) with moderate/severe HIE on non-servocontrolled therapeutic hypothermia by the two neonatal transport teams in Catalonia. RESULTS: 51 newborns. The median stabilisation and transport time were 68 min (p25-75, 45-85 min) and 30 min (p25-75, 15-45 min), respectively. The mean age at arrival at the receiving unit was 4 h and 18 min (SD 96.6). The incubator was set off in 43 (84%), iced-packs 11 (21.5%) and both (11, 21.5%). Target temperature was reached in 19 (37.3%) babies. There were no differences in the overcooling in relation to the measures applied. The transport duration was not related with temperature stabilisation or target temperature reachiness. CONCLUSIONS: Rectal temperature monitorisation is compulsory for the stabilisation and the application of non-servocontrolled hypothermia during transport. There is still time for improving in the administration of this treatment during transport. Servo-controlled hypothermia would be a better alternative to improve the management of HIE babies.

[Challenges in the application of non-servocontrolled therapeutic hypothermia during neonatal transport in Catalonia]. / Retos en la aplicación de la hipotermia terapéutica no servo-controlada durante el transporte neonatal en Cataluña.

INTRODUCTION: Therapeutic hypothermia (TH) improves survival and neurological prognosis in hypoxic-ischemic encephalopathic (HIE) babies, being better the sooner TH is implemented. HIE babies are born more frequently in a non-cooling centre and need to be referred. METHODS: Prospective-observational study (April 18-November 19). Newborns (≥34 weeks of gestational age (GA) and >1800g) with moderate/severe HIE on non-servocontrolled therapeutic hypothermia by the two neonatal transport teams in Catalonia. RESULTS: 51 newborns. The median stabilisation and transport time were 68min (p25-75, 45-85min) and 30min (p25-75, 15-45min), respectively. The mean age at arrival at the receiving unit was 4h and 18min (SD 96.6). The incubator was set off in 43 (84%), iced-packs 11 (21.5%) and both (11, 21.5%). Target temperature was reached in 19 (37.3%) babies. There was no differences in the overcooling in relation to the measures applied. The transport duration was not related with temperature stabilisation or target temperature reachiness. CONCLUSIONS: Rectal temperature monitorisation is compulsory for the stabilisation and the application of non-servocontrolled hypothermia during transport. There is still time for improving in the administration of this treatment during transport. Servo-controlled hypothermia would be a better alternative to improve the management of HIE babies.

Interferon-Gamma Release Assays Differentiate between Mycobacterium avium Complex and Tuberculous Lymphadenitis in Children.

OBJECTIVES: To assess the performance of interferon-gamma release assays (IGRAs) in the differential diagnosis between Mycobacterium avium complex (MAC) and tuberculosis (TB) in children affected with subacute/chronic submandibular/cervical lymphadenitis. STUDY DESIGN: Multicenter observational study comparing children with microbiologically confirmed MAC lymphadenitis from the European NontuberculouS MycoBacterial Lymphadenitis in childrEn study with children with TB lymphadenitis from the Spanish Network for the Study of Pediatric TB database. RESULTS: Overall, 78 patients with MAC and 34 with TB lymphadenitis were included. Among MAC cases, 44 out of 74 (59.5%) had positive tuberculin skin test (TST) results at the 5-mm cut-off, compared with 32 out of 33 (97%) TB cases (P < .001); at the 10-mm cut-off TST results were positive in 23 out of 74 (31.1%) vs 26 out of 31 (83.9%), respectively (P < .001). IGRA results were positive in only 1 out of 32 (3.1%) patients with MAC who had undergone IGRA testing, compared with 21 out of 23 (91.3%) TB cases (P < .001). Agreement between TST and IGRA results was poor in MAC (23.3%; κ = 0.017), but good in TB cases (95.6%; κ = 0.646). IGRAs had a specificity of 96.9% (95% CI 84.3%-99.8%), positive predictive value of 95.4% (95% CI 78.2%-99.8%), and negative predictive value of 93.9% (95% CI 80.4%-98.9%) for TB lymphadenitis. CONCLUSIONS: In contrast to TST, IGRAs have high specificity, negative predictive value, and positive predictive value for TB lymphadenitis in children with subacute/chronic lymphadenopathy, and consequently can help to discriminate between TB and MAC disease. Therefore, IGRAs are useful tools in the diagnostic work-up of children with lymphadenopathy, particularly when culture and polymerase chain reaction results are negative.

Noninvasive Respiratory Support During Pediatric Ground Transport: Implementation of a Safe and Feasible Procedure.

BACKGROUND: The purpose of this work was to determine the safety and feasibility of noninvasive support in children with acute respiratory failure (ARF) during interhospital ground transport. METHODS: This was a prospective, single-center observational clinical study in the pediatric transport unit of a tertiary-care pediatric hospital. We included all subjects with ARF transported from November 2010 to March 2013. A specific noninvasive support protocol was used for all cases. Transport ventilators used were the Crossvent 2+ and Oxylog 3000; interfaces were an oronasal mask, nasopharyngeal tube, or nasal prongs. RESULTS: A total of 288 children diagnosed with ARF were transported. Fifty-four subjects (19%) were transported with invasive ventilation, 50 with CPAP, 58 with NIV, and 126 (44%) with oxygen cannula or nebulization. The median age was 3.4 months (interquartile range 1.2-17 months). ARF was mainly due to bronchiolitis (58%), asthma (15%), and pneumonia (15%). Stabilization time, which is defined as the time between the arrival in the parking lot of the referring hospital and departure, was lower with noninvasive support than with invasive ventilation (median 48 min vs 83 min, P < .001). Median transport time was 35 min (interquartile range 20-65). Noninvasive ventilation and oronasal interface use rose progressively during the study period (P < .001 for the NIV and P < .036 for the interface). One complication was observed: One subject required intubation during transport. Evolution of subjects transferred while receiving noninvasive support was recorded in the receptor hospitals: 21% of subjects were intubated, and 55% continued with NIV. CONCLUSIONS: NIV seems to be a safe and feasible technique during pediatric ground transport. Careful patient selection, adequate material, and a well-trained transport team are crucial to minimize risks to the patient.

Clinical characteristics and molecular epidemiology of Enterovirus infection in infants <3 months in a referral paediatric hospital of Barcelona.

UNLABELLED: Enterovirus (EV) infection is common in infants, but the information with regard to the molecular epidemiology and the associations between types and clinical variables is very scarce. This study includes 195 children <3 months old with fever, attended from March 2010 to December 2012 in an emergency department of a tertiary paediatric hospital in whom EV infection was confirmed by real-time PCR in blood and/or cerebrospinal fluid. Clinical and epidemiological data was prospectively collected. In 152 (77.9 %) patients, EVs could be typed. The most common type was Echovirus-5 (E5; 32, 21.1 %), followed by Echovirus-11 (E11; 18, 11.8 %), Echovirus-21 and Echovirus-25 (E21, E25; 11 each one, 7.2 %) and Coxsackievirus-B4 (CVB4; 6, 6.6 %). The majority of types appeared in spring, but E5 and E25 were found mainly during summer (p < 0.01). E21 was associated with high-grade fever (p < 0.01); E5 with exanthema (p = 0.03) and CVB4 tended to cause meningitis more often than the other types (p = 0.07). CONCLUSION: The most common EV types were Echovirus-5 and Echovirus-11. Some significant associations between types and epidemiologic and clinical findings were observed. What is Known-What is New • Enteroviruses cause a normally benign illness in young infants, except in some cases. • The molecular epidemiology of Enterovirus infection is not well known in European countries. • This study describes a large number of infants with Enterovirus infection and shows the seasonality of different types, and their associations with epidemiologic and clinical variables.

2009 H1N1: risk factors for hospitalization in a matched case-control study.

In order to compare sociodemographical data and preexisting risk medical conditions in patients requiring hospital admission for 2009 pandemic influenza A (H1N1) virus infection and those managed on an outpatient basis, a prospective observational, matched case-control study in 36 hospitals of the Spanish National Health Service was conducted from July 2009 to February 2010. Cases were patients aged 6 months to 18 years hospitalized for influenza syndrome, in whom 2009 influenza A (H1N1) virus infection was confirmed using real-time reverse-transcription polymerase chain reaction. Controls were patients aged 6 months to 18 years with confirmed 2009 influenza A (H1N1) infection managed on an outpatient basis. There were 195 cases and 184 controls. In a multivariate model, hospitalization was more frequent in children aged <2 years (odds ratio (OR), 13.8; 95% confidence interval (CI), 1.7-106.4), those with neurological and/or neuromuscular diseases (OR, 3.0; 95% CI, 1.1-8.2), and those whose parents had less than a secondary educational level (OR, 2.7; 95% CI, 1.4-5.2). Children aged <2 years, children with neurological diseases, and children from families with a lower educational status had a higher risk of hospitalization due to influenza A (H1N1) 2009 infection.

2009 Influenza A H1N1 infections: delays in starting treatment with oseltamivir were associated with a more severe disease.

Respiratory failure has been the main severe complication described in pediatric patients with influenza A H1N1 2009 (pandemic H1N1) infection. We describe the pandemic H1N1 2009 disease in children who required hospital admission and the patients' data associated with pediatric intensive care unit admission. Respiratory failure was the main complication. Extrapulmonary manifestations were also observed. Of the 127 patients, 24 required pediatric intensive care unit admission. Four patients died. Patients admitted with chronic conditions and those in whom oseltamivir was delayed more than 72 hours had a more severe disease.