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 (ENSeMBLE) study with children with TB lymphadenitis from the Spanish Network for the Study of Pediatric TB (pTBred) database. RESULTS: Overall, 78 patients with MAC and 34 with TB lymphadenitis were included. Among MAC cases, 44/74 (59.5%) had positive tuberculin skin test (TST) results at the 5 mm cutoff, compared with 32/33 (97%) TB cases (p<0.001); at the 10 mm cutoff TST results were positive in 23/74 (31.1%) vs. 26/31 (83.9%), respectively (P < .001). IGRA results were positive in only 1/32 (3.1%) MAC cases who had undergone IGRA testing, compared with 21/23 (91.3%) TB cases (p<0.001). 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 (PPV) of 95.4% (95%CI:78.2-99.8%), and negative predictive value (NPV) of 93.9% (95%CI:80.4-98.9%) for TB lymphadenitis. CONCLUSIONS: In contrast to TST, IGRAs have high specificity, NPV and PPV 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 PCR-results are negative

Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals

Background & Aims: Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. Methods: SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results: The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. Conclusions: Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized. Lay summary: Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses

Social factors related to the clinical severity of influenza cases in Spain during the A(H1N1)2009 virus pandemic

Background During the 2009 influenza pandemic, a change in the type of patients most often affected by influenza was observed. The objective of this study was to assess the role of individual and social determinants in hospitalizations due to influenza A (H1N1) 2009 infection. Methods We studied hospitalized patients (cases) and outpatients (controls) with confirmed influenza A (H1N1) 2009 infection. A standardized questionnaire was used to collect data. Variables that might be related to the hospitalization of influenza cases were compared by estimation of the odds ratio (OR) and 95% confidence intervals (CI) and the variables entered into binomial logistic regression models. Results Hospitalization due to pandemic A (H1N1) 2009 influenza virus infections was associated with non-Caucasian ethnicity (OR: 2.18, 95% CI 1.17 − 4.08), overcrowding (OR: 2.84, 95% CI 1.20 − 6.72), comorbidity and the lack of previous preventive information (OR: 2.69, 95% CI: 1.50 − 4.83). Secondary or higher education was associated with a lower risk of hospitalization (OR 0.56, 95% CI: 0.36 − 0.87) Conclusions In addition to individual factors such as comorbidity, other factors such as educational level, ethnicity or overcrowding were associated with hospitalization due to A (H1N1) 2009 influenza virus infections

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Treatment and outcomes in children with multidrug-resistant tuberculosis: a systematic review and individual patient data meta-analysis.

CAPRISA, 2018.Abstract available in pdf

High Rates of SARS-CoV-2 Family Transmission in Children of Healthcare Workers During the First Pandemic Wave in Madrid, Spain: Serologic Study.

Data on SARS-CoV-2 transmission among children living with healthcare workers (HCWs) are scarce. A cross-sectional study was performed at a tertiary Hospital in Madrid, including children of HCW who suffered from SARS-CoV-2 infection between March and May 2020. Children underwent enzyme-linked immunosorbent serological study for detecting SARS-CoV-2 antibodies: VIRCELL IgG assay. One hundred thirteen children from 69 HCWs with confirmed SARS-CoV-2 infection were recruited: 47 children had positive IgG (41.6%). Children secondary attack rate was 43.7% (25% if both parents have had asymptomatic infection; 39.5% if one parent was symptomatic; and 47% when both parents had symptoms). Having a positive sibling was associated with a positive IgG result (odds ratio = 12.2; 95% confidence interval: 4.4-33.7, P We observed a very high SARS-CoV-2 transmission in children of HCW during the first pandemic wave, especially when both parents were symptomatic. Having a positive sibling was associated with seroconversion, supporting the important role of family clusters in the transmission of SARS-CoV-2

Multiplex PCR and Antibiotic Use in Children with Community-Acquired Pneumonia

Antibiotics are frequently prescribed to children with pneumonia, although viruses are responsible for most cases. We aimed to evaluate the impact of multiplex polymerase chain reaction (mPCR) on antibiotic use. We conducted a prospective study of children under 14 years of age admitted for suspected viral pneumonia, from October 2019 to June 2022 (except March–November 2020). A mPCR respiratory panel (FilmArray® 2plus, bioMérieux, Marcy-l’Étoile, France) was performed within 72 h of admission. Patients with positive reverse transcription PCR for respiratory syncytial virus, influenza, or SARS-CoV-2 were excluded. We compared the patients with historical controls (2017–2018) who had suspected viral pneumonia but did not undergo an aetiological study. We included 64 patients and 50 controls, with a median age of 26 months. The respiratory panel detected viral pathogens in 55 patients (88%), including 17 (31%) with co-infections. Rhinovirus/enterovirus (n = 26) and human metapneumovirus (n = 22) were the most common pathogens, followed by adenovirus and parainfluenza (n = 10). There were no statistically significant differences in the total antibiotic consumption (83% of cases and 86% of controls) or antibiotics given for ≥72 h (58% vs. 66%). Antibiotics were prescribed in 41% of the cases and 72% of the controls at discharge (p = 0.001). Ampicillin was the most commonly prescribed antibiotic among the patients (44% vs. 18% for controls, p = 0.004), while azithromycin was the most commonly prescribed among the controls (19% vs. 48% for patients and controls, respectively; p = 0.001). Our findings underscore the need for additional interventions alongside molecular diagnosis to reduce antibiotic usage in paediatric community-acquired pneumonia

Update on the diagnosis and treatment of tuberculosis

According to World Health Organization estimates, more than 1 million patients aged less than 15 years develop tuberculosis (TB) each year worldwide. In some regions, up to 25% of new TB cases are caused by drug-resistant strains. Although Spain is considered a low-incidence country, several hundred children and adolescents develop TB each year. The importance of paediatric TB has been minimized for years due to the lack of microbiological confirmation in many patients and because these patients are not usually contagious. Nevertheless, in the past 15 years there have been major improvements in the epidemiological reporting of TB in children and adolescents, new immunodiagnostic tests have been developed, molecular methods that allow rapid microbiological diagnosis and detection of variants associated with drug resistance have become available, novel second-line antituberculosis drugs have been discovered, including for paediatric use, and the results of clinical trials have validated shorter courses of treatment for some patients. This document, developed by a group of experts from the Sociedad Española de Infectología Pediátrica and the Sociedad Española de Neumología Pediátrica, updates and complements the previous guidelines for the diagnostic and therapeutic management of children with TB in Spain based on the newly available scientific evidence. Resumen: Más de un millón de pacientes menores de 15 años desarrollan tuberculosis (TB) anualmente en el Mundo, según estimaciones de la Organización Mundial de Salud. La TB por cepas resistentes a los fármacos de primera línea alcanza al 25% de los nuevos casos en algunas regiones. Aunque España es considerada un país de baja incidencia, varios centenares de niños y adolescentes enferman de TB cada año. La importancia de la TB pediátrica ha sido minimizada durante años por la dificultad en confirmar el diagnóstico microbiológico y la escasa contagiosidad que asocia. Sin embargo, en los últimos 15 años, se han reportado mejoras relevantes en los informes epidemiológicos de la TB en niños y adolescentes, han surgido nuevos tests inmunodiagnósticos, se dispone de estudios de biología molecular que permiten un diagnóstico microbiológico y una identificación de mutaciones asociadas a resistencia rápidos, han surgido nuevos fármacos antituberculosos de segunda línea, también en pediatría, y se han publicado ensayos clínicos que validan tratamientos acortados en algunos pacientes. Este documento, realizado por un grupo de expertos de la Sociedad Española de Infectología Pediátrica y la Sociedad Española de Neumología Pediátrica, actualiza y complementa las recomendaciones previas para el manejo diagnóstico y terapéutico del niño con TB en España, en base a las nuevas evidencias científicas disponibles