Publications by authors named "Clàudia Fortuny"

102 Publications

Renal Involvement in Congenital Cytomegalovirus Infection: A Systematic Review.

Microorganisms 2021 Jun 15;9(6). Epub 2021 Jun 15.

Malalties Infeccioses i Resposta Inflamatòria Sistèmica en Pediatria, Unitat d'Infeccions, Servei de Pediatria, Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain.

Background: Congenital cytomegalovirus (cCMV) infection is the most frequent mother-to-child transmitted infection worldwide and a prevalent cause of neonatal disease and long-term morbidity. The kidney is a target organ for CMV, which replicates in renal tubules and is excreted in large quantities in urine for years in children with cCMV infection. Nonetheless, kidney disease has rarely been reported in cCMV-infected patients.

Objective: We aimed to describe the available data on renal involvement in patients with cCMV infection at the pathologic, functional, anatomical, and/or clinical levels.

Methods: A systematic search was performed in the MEDLINE/PubMed, SCOPUS, and Cochrane databases. Studies describing any renal involvement in fetuses or neonates aged ≤3 weeks at diagnosis of microbiologically confirmed cCMV infection were eligible.

Results: Twenty-four articles were included, with a very low level of evidence. Pathologic findings in autopsy studies universally described CMV typical inclusion bodies in tubular cells. No functional studies were identified. cCMV infection was not associated with an increased risk of kidney malformations. Congenital nephrotic syndrome was the most common clinical condition associated with cCMV, but a causal relationship cannot be established.

Conclusions: Typical pathological features of cCMV infection are very common in renal tissue, but they do not seem to entail significant consequences at the anatomical or clinical levels.
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http://dx.doi.org/10.3390/microorganisms9061304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232607PMC
June 2021

Impact and quality of antimicrobial use in a referral pediatric intensive care unit.

Enferm Infecc Microbiol Clin 2021 Jun 12. Epub 2021 Jun 12.

Infectious Diseases and Systemic Inflammatory Response in Pediatrics, Infectious Diseases Unit, Department of Pediatrics, Institut de Recerca Sant Joan de Déu, Barcelona, Spain; Centre for Biomedical Network Research on Epidemiology and Public Health, CIBERESP, Madrid, Spain; Red de Investigación Translacional en Infectología Pediátrica, RITIP, Madrid, Spain; Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain. Electronic address:

Introduction: We aimed to describe antimicrobial use (AU) and quality of prescriptions (QP) in a 28-bed medical-surgical PICU of a European referral children's hospital during 2019.

Methods: AU data were expressed as days-of-therapy (DOT) over 100 days-present (DP) and as length-of-treatment (LOT). QP was based on monthly cross-sectional point-prevalence surveys. Length-of-stay (LOS), readmission rates (RR), and mortality rates (MR) were also collected.

Results: PICU AU accounted for 13.5% of the global hospital AU; the median PICU density of AU was 1.4 (IQR 1.3-1.5) times higher than that of the rest of the hospital areas. Antibacterials represented 88.5% of the overall AU, cefazolin and amoxicillin-clavulanate being the most used drugs. A high QP rate was observed (149/168 optimal, 88.9%), with room for improvement in prophylactic regimens and de-escalation of broad-spectrum regimens. LOT, LOS, RR, and MR remained stable.

Conclusions: PICU AU represented a major portion of the global hospital AU. Despite high QP rates, prophylactic and broad-spectrum antibiotic regimens were optimizable.
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http://dx.doi.org/10.1016/j.eimc.2021.05.001DOI Listing
June 2021

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

J Pediatr 2021 Sep 10;236:211-218.e2. Epub 2021 May 10.

Infectious Diseases and Systemic Inflammatory Response in Pediatrics, Infectious Diseases Unit, Department of Pediatrics, Institut de Recerca Sant Joan de Déu, Barcelona, Spain; Translational Research Network of Pediatric Infectious Diseases (RITIP), Madrid, Spain; Center for Biomedical Network Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Pediatrics, University of Barcelona, Barcelona, Spain. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jpeds.2021.05.008DOI Listing
September 2021

A Mitocentric View of the Main Bacterial and Parasitic Infectious Diseases in the Pediatric Population.

Int J Mol Sci 2021 Mar 23;22(6). Epub 2021 Mar 23.

Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.

Infectious diseases occur worldwide with great frequency in both adults and children. Both infections and their treatments trigger mitochondrial interactions at multiple levels: (i) incorporation of damaged or mutated proteins to the complexes of the electron transport chain, (ii) mitochondrial genome (depletion, deletions, and point mutations) and mitochondrial dynamics (fusion and fission), (iii) membrane potential, (iv) apoptotic regulation, (v) generation of reactive oxygen species, among others. Such alterations may result in serious adverse clinical events with great impact on children's quality of life, even resulting in death. As such, bacterial agents are frequently associated with loss of mitochondrial membrane potential and cytochrome c release, ultimately leading to mitochondrial apoptosis by activation of caspases-3 and -9. Using Rayyan QCRI software for systematic reviews, we explore the association between mitochondrial alterations and pediatric infections including (i) bacterial: , and (ii) parasitic: . We analyze how these pediatric infections and their treatments may lead to mitochondrial deterioration in this especially vulnerable population, with the intention of improving both the understanding of these diseases and their management in clinical practice.
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http://dx.doi.org/10.3390/ijms22063272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004694PMC
March 2021

Mitochondrial changes associated with viral infectious diseases in the paediatric population.

Rev Med Virol 2021 Mar 31:e2232. Epub 2021 Mar 31.

Faculty of Medicine and Health Sciences, Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, University of Barcelona, Barcelona, Spain.

Infectious diseases occur worldwide with great frequency in both adults and children, causing 350,000 deaths in 2017, according to the latest World Health Organization reports. Both infections and their treatments trigger mitochondrial interactions at multiple levels: (i) incorporation of damaged or mutated proteins into the complexes of the electron transport chain; (ii) impact on mitochondrial genome (depletion, deletions and point mutations) and mitochondrial dynamics (fusion and fission); (iii) membrane potential impairment; (iv) apoptotic regulation; and (v) generation of reactive oxygen species, among others. Such alterations may result in serious adverse clinical events with considerable impact on the quality of life of the children and could even cause death. Herein, we use a systematic review to explore the association between mitochondrial alterations in paediatric infections including human immunodeficiency virus, cytomegalovirus, herpes viruses, various forms of hepatitis, adenovirus, T-cell lymphotropic virus and influenza. We analyse how these paediatric viral infectious processes may cause mitochondrial deterioration in this especially vulnerable population, with consideration for the principal aspects of research and diagnosis leading to improved disease understanding, management and surveillance.
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http://dx.doi.org/10.1002/rmv.2232DOI Listing
March 2021

Transmission of SARS-CoV-2 infection among children in summer schools applying stringent control measures in Barcelona, Spain.

Clin Infect Dis 2021 Mar 12. Epub 2021 Mar 12.

NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research Centre, University Hospital NHS Foundation Trust; and Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.

Background: Understanding the role of children in SARS-CoV-2 transmission is critical to guide decision-making for schools in the pandemic. We aimed to describe the transmission of SARS-CoV-2 among children and adult staff in summer schools.

Methods: During July 2020 we prospectively recruited children and adult staff attending summer schools in Barcelona who had SARS-CoV-2 infection. Primary SARS-CoV-2 infections were identified through: (1) surveillance program in 22 summer schools' of 1905 participants, involving weekly saliva sampling for SARS-CoV-2 RT-PCR during 2-5 weeks; (2)cases identified through the Catalonian Health Surveillance System of children diagnosed with SARS-CoV-2 infection by nasopharyngeal RT-PCR. All centres followed prevention protocols: bubble groups, hand washing, facemasks and conducting activities mostly outdoors. Contacts of a primary case within the same bubble were evaluated by nasopharyngeal RT-PCR. Secondary attack rates and effective reproduction number in summer schools(R*) were calculated.

Results: Among the over 2000 repeatedly screened participants, 30children and 9adults were identified as primary cases. A total of 253 close contacts of these primary cases were studied (median 9 (IQR 5-10) for each primary case), among which twelve new cases (4.7%) were positive for SARS-CoV-2. The R* was 0.3, whereas the contemporary rate in the general population from the same areas in Barcelona was 1.9.

Conclusions: The transmission rate of SARS-CoV-2 infection among children attending school-like facilities under strict prevention measures was lower than that reported for the general population. This suggests that under preventive measures schools are unlikely amplifiers of SARS-CoV-2 transmission and supports current recommendations for school opening.
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http://dx.doi.org/10.1093/cid/ciab227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989514PMC
March 2021

Zika virus infection in pregnant travellers and impact on childhood neurodevelopment in the first two years of life: A prospective observational study.

Travel Med Infect Dis 2021 Mar-Apr;40:101985. Epub 2021 Feb 15.

ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique. Electronic address:

Background: The emergence of Zika virus (ZIKV) represents a threat with consequences on maternal and children's health. We aimed to assess the clinical and epidemiological characteristics of pregnant women returning from ZIKV affected areas, and the effects of maternal ZIKV infection on birth outcomes and children's health.

Methods: This was a hospital-based prospective observational study conducted at the Hospital Clínic of Barcelona and Hospital Sant Joan de Déu, Barcelona, Spain, from January 2016 to February 2020.

Results: One hundred and ninety-five pregnant women who had travelled to ZIKV affected areas during pregnancy were recruited. Four women (2.1%) had a confirmed ZIKV infection, 40 women (20.5%) a probable infection, and 151 (77.4%) were negative for ZIKV. Among the ZIKV confirmed cases, a pregnant woman suffered a miscarriage, highly plausible to be associated with ZIKV infection. Brain cysts and microcalcifications were detected in 7% of fetuses or infants from women with confirmed or probable ZIKV infection. Neurodevelopmental delay in the language function was found in 33.3% out of the 21 children evaluated.

Conclusions: These findings contribute to the understanding of ZIKV prevalence estimates, and the impact of maternal ZIKV infection on pregnancy outcomes and children's health. Results highlight the importance of long-term surveillance in pregnant travellers and their children.
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http://dx.doi.org/10.1016/j.tmaid.2021.101985DOI Listing
September 2021

Similarities and differences between the immunopathogenesis of COVID-19-related pediatric multisystem inflammatory syndrome and Kawasaki disease.

J Clin Invest 2021 03;131(6)

Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu (HSJD), Barcelona, Spain.

Multisystem inflammatory syndrome associated with the SARS-CoV-2 pandemic has recently been described in children (MIS-C), partially overlapping with Kawasaki disease (KD). We hypothesized that (a) MIS-C and prepandemic KD cytokine profiles may be unique and justify the clinical differences observed, and (b) SARS-CoV-2-specific immune complexes (ICs) may explain the immunopathology of MIS-C. Seventy-four children were included: 14 with MIS-C, 9 patients positive for SARS-CoV-2 by PCR without MIS-C (COVID), 14 with prepandemic KD, and 37 healthy controls (HCs). Thirty-four circulating cytokines were quantified in pretreatment serum or plasma samples and the presence of circulating SARS-CoV-2 ICs was evaluated in MIS-C patients. Compared with HCs, the MIS-C and KD groups showed most cytokines to be significantly elevated, with IFN-γ-induced response markers (including IFN-γ, IL-18, and IP-10) and inflammatory monocyte activation markers (including MCP-1, IL-1α, and IL-1RA) being the main triggers of inflammation. In linear discriminant analysis, MIS-C and KD profiles overlapped; however, a subgroup of MIS-C patients (MIS-Cplus) differentiated from the remaining MIS-C patients in IFN-γ, IL-18, GM-CSF, RANTES, IP-10, IL-1α, and SDF-1 and incipient signs of macrophage activation syndrome. Circulating SARS-CoV-2 ICs were not detected in MIS-C patients. Our findings suggest a major role for IFN-γ in the pathogenesis of MIS-C, which may be relevant for therapeutic management.
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http://dx.doi.org/10.1172/JCI144554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954607PMC
March 2021

Cardiac Remodeling and Hypertension in HIV-Uninfected Infants Exposed in utero to Antiretroviral Therapy.

Clin Infect Dis 2021 Aug;73(4):586-593

Fetal Medicine Research Center, BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), Institut Clinic de Ginecologia, Obstetricia i Neonatologia (ICGON), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.

Background: We aimed to assess the postnatal pattern of cardiovascular remodeling associated with intrauterine exposure to maternal HIV and antiretroviral treatment (ART).

Methods: Prospective cohort including 34 HIV-exposed uninfected (HEU) infants and 53 non-HIV-exposed infants were evaluated from fetal life up to 6 months postnatally. A cardiovascular evaluation was performed including echocardiography, blood pressure, and carotid intima media thickness (cIMT) measurement.

Results: ART regimens during pregnancy included 2 nucleoside reverse transcriptase inhibitors (Abacavir + Lamivudine (32.4%), Emtricitabine + Tenofovir (41.2%), and Zidovudine + Lamivudine (20.6%)). At 6 months of age, HIV-exposed uninfected infants showed thicker myocardial walls (septal wall thickness mean 5.02 mm (SD 0.85) vs 3.98 mm (0.86); P < .001), relative systolic dysfunction with decreased mitral ring displacement (8.57 mm (2.03) vs 10.34 mm (1.84); P = .002), and decreased tricuspid S' (9.71 cm/s (1.94) vs 11.54 cm/s (2.07); P = .003) together with relative diastolic dysfunction showed by prolonged left isovolumic relaxation time (58.57 ms (13.79) vs 47.94 (7.39); P < .001). Vascular assessment showed significantly higher systolic and diastolic blood pressure (102 mmHg (16.1) vs 80 mmHg (13.9); P < .001 and 64 mmHg (14.4) vs 55 mmHg (10.2); P = .045 respectively), with 50% of HIV-exposed children meeting criteria for hypertension vs 3.77% of the non-HIV-exposed group (P < .001) and thicker mean cIMT in the HIV-exposed group (0.62 µm (0.09) vs 0.51 µm (0.09); P = .015).

Conclusions: Subclinical cardiac impairment together with higher blood pressure and thicker cIMT were observed in HIV-exposed infants at 6 months of age. Half of them presented hypertension. Our findings support a possible increased cardiovascular risk in HIV uninfected infants exposed in utero to ART.
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http://dx.doi.org/10.1093/cid/ciab030DOI Listing
August 2021

Weight-adapted fixed-dose combined adult antiretroviral tablets for HIV-infected children.

J Clin Pharm Ther 2021 Aug 4;46(4):867-871. Epub 2021 Jan 4.

Hospital Sant Joan de Deu, Malalties Infeccioses i Resposta Inflamatòria Sistèmica en Pediatria, Universitat de Barcelona, Pediatria, Red de Investigación Translacional en Infectología Pediátrica, RITIP, Barcelona, Spain.

What Is Known And Objective: Therapeutic alternatives to simplify antiretroviral therapy (ART) in HIV-infected children are needed. We report our experience with abacavir(ABC)/lamivudine(3TC) individualized dose compounded capsules (IDCC).

Comment: We present a prospective case series of HIV-infected children who did not weigh enough to receive the adult fixed-dose combination including ABC/3TC 600mg/300mg, and were treated with weight-adapted ABC/3TC IDCC in Barcelona, Spain. Thirteen patients (12 girls) received ABC/3TC IDCC for a median(IQR) time of 30(17-54) months. No significant changes were observed in CD4 cell counts, weight or height z-scores over time. Suppression of viral replication was maintained in 7 patients with undetectable viremia at baseline. Another 5 patients achieved viral suppression with ABC/3TC IDCC-based ART, while one non-adherent girl did not. No adverse events related to ABC/3TC IDCC were observed.

What Is New And Conclusion: Despite small numbers, the long-term use of ABC/3TC IDCC was feasible, safe, and effective in the treatment of HIV-infected children.
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http://dx.doi.org/10.1111/jcpt.13341DOI Listing
August 2021

Effects of a Paediatric Antimicrobial Stewardship Program on Antimicrobial Use and Quality of Prescriptions in Patients with Appendix-Related Intraabdominal Infections.

Antibiotics (Basel) 2020 Dec 23;10(1). Epub 2020 Dec 23.

Infectious Diseases and Systemic Inflammatory Response in Paediatrics, Infectious Diseases Unit, Department of Paediatrics, Sant Joan de Déu Hospital Research Foundation, 08950 Barcelona, Spain.

The effectiveness of antimicrobial stewardship programs (ASP) in reducing antimicrobial use (AU) in children has been proved. Many interventions have been described suitable for different institution sizes, priorities, and patients, with surgical wards being one of the areas that may benefit the most. We aimed to describe the results on AU and length of stay (LOS) in a pre-post study during the three years before (2014-2016) and the three years after (2017-2019) implementation of an ASP based on postprescription review with feedback in children and adolescents admitted for appendix-related intraabdominal infections (AR-IAI) in a European Referral Paediatric University Hospital. In the postintervention period, the quality of prescriptions (QP) was also evaluated. Overall, 2021 AR-IAIs admissions were included. Global AU, measured both as days of therapy/100 patient days (DOT/100PD) and length of therapy (LOT), and global LOS remained unchanged in the postintervention period. Phlegmonous appendicitis LOS ( = 0.003) and LOT ( < 0.001) significantly decreased, but not those of other AR-IAI diagnoses. The use of piperacillin-tazobactam decreased by 96% ( = 0.044), with no rebound in the use of other Gram-negative broad-spectrum antimicrobials. A quasisignificant ( = 0.052) increase in QP was observed upon ASP implementation. Readmission and case fatality rates remained stable. ASP interventions were safe, and they reduced LOS and LOT of phlegmonous appendicitis and the use of selected broad-spectrum antimicrobials, while increasing QP in children with AR-IAI.
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http://dx.doi.org/10.3390/antibiotics10010005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822420PMC
December 2020

Maternal high-dose valacyclovir and its correlation with newborn blood viral load and outcome in congenital cytomegalovirus infection.

J Matern Fetal Neonatal Med 2020 Nov 3:1-5. Epub 2020 Nov 3.

Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu). Institut Clínic de Ginecología, Obstetricia i Neonatologia, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain.

Background/objective: Currently, there is no validated treatment for fetal cytomegalovirus (CMV). Two studies suggest that high-dose maternal valacyclovir decreases fetal viral load and improves outcomes in moderately-symptomatic fetuses. We offered valacyclovir in cases of fetal infection lacking ultrasound abnormalities or with non-severe infection. Maternal tolerability, fetal outcome and newborn blood viral load were evaluated in pregnancies of mothers receiving valacyclovir.

Study Design: We performed a case series including 8 pregnancies with fetal CMV classified as unaffected/mildly-moderately affected. Mothers received valacyclovir (8 g/24h) from fetal infection diagnosis to delivery. Standard newborn evaluation was performed, and viremia was determined in the first 48 h of life and compared according to length of maternal treatment and presence/absence of prenatal anomalies.

Results: Valacyclovir was administered at a median gestational age of 26.5 weeks (23.8-33.1) in 3 cases without fetal abnormalities, and 5 with mild/moderate abnormalities. Three were 3 first trimester primary infections, one non-primary infection, and in 4 the type of infection was unknown. Valacyclovir was well-tolerated. Fetal features did not progress. Three newborns were asymptomatic, and one was severely affected (bilateral chorioretinitis). The median newborn viral load (IQR) was 502 IU/mL (231-191781) with lower levels when maternal treatment was administered ≥10 weeks, and in cases without fetal abnormalities [median 234 IU/mL (228-711) vs. 4061 (292-510500)  = .18; and 234 IU/mL (228-379500) vs. 711 IU/mL (292-4061)  = .65, respectively], these differences being non-significant.

Conclusions: Fetal CMV lesions remained stable with high-dose maternal valacyclovir. Newborn viral load was unchanged despite treatment duration and fetal/neonatal abnormalities.

Summary: Fetal cytomegalovirus lesions remained stable with high-dose maternal valacyclovir. Newborn viral load was unchanged despite treatment duration and fetal/newborn abnormalities.
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http://dx.doi.org/10.1080/14767058.2020.1843016DOI Listing
November 2020

Low impact of SARS-CoV-2 infection among paediatric acute respiratory disease hospitalizations.

J Infect 2021 03 21;82(3):414-451. Epub 2020 Oct 21.

Paediatrics Department, Hospital Sant Joan de Déu (HSJD), Barcelona, Spain; University of Barcelona, Barcelona, Spain; Paediatric Infectious Diseases Research Group, Institut de Recerca Sant Joan de Déu, Barcelona, Spain; CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. Electronic address:

Objective: This study describes the characteristics of children requiring admission with an acute lower-respiratory disease (ALRD) during the SARS-CoV-2 pandemics.

Methods: Epidemiological, clinical, and microbiological data from patients with ALRD (pneumonia, bronchiolitis, bronchospasm) admitted to a reference paediatric hospital in Spain during the pandemic peak (week 11-20/2020) were prospectively analysed.

Results: 110 patients were included. 7 were SARS-CoV-2(+) and they were older in comparison to SARS-CoV-2(-). Among SARS-CoV-2(+) patients, pneumonia was the main clinical diagnosis (6/7) and bronchospasm was absent. Only 1 of 29 infants diagnosed with bronchiolitis was SARS-CoV-2(+). Lower values of leucocytes, lymphocytes, neutrophils, and platelets and higher values of creatinine were found in SARS-CoV-2(+). Human-rhinovirus/enterovirus was the main detection (11/32). There were not differences in PICU admission rates between SARS-CoV-2(+) and (-).

Conclusions: Most of the ALRD episodes identified during the pandemics were not related to SARS-CoV-2 infection. SARS-CoV-2 was mainly found causing pneumonia in older children.
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http://dx.doi.org/10.1016/j.jinf.2020.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577222PMC
March 2021

Severe Autoinflammatory Manifestations and Antibody Deficiency Due to Novel Hypermorphic PLCG2 Mutations.

J Clin Immunol 2020 10 15;40(7):987-1000. Epub 2020 Jul 15.

Department of Immunology-CDB (esc 4-pl 0), Hospital Clínic, Villarroel, 170, 08036, Barcelona, Spain.

Autoinflammatory diseases (AIDs) were first described as clinical disorders characterized by recurrent episodes of seemingly unprovoked sterile inflammation. In the past few years, the identification of novel AIDs expanded their phenotypes toward more complex clinical pictures associating vasculopathy, autoimmunity, or immunodeficiency. Herein, we describe two unrelated patients suffering since the neonatal period from a complex disease mainly characterized by severe sterile inflammation, recurrent bacterial infections, and marked humoral immunodeficiency. Whole-exome sequencing detected a novel, de novo heterozygous PLCG2 variant in each patient (p.Ala708Pro and p.Leu845_Leu848del). A clear enhanced PLCγ2 activity for both variants was demonstrated by both ex vivo calcium responses of the patient's B cells to IgM stimulation and in vitro assessment of PLC activity. These data supported the autoinflammation and PLCγ2-associated antibody deficiency and immune dysregulation (APLAID) diagnosis in both patients. Immunological evaluation revealed a severe decrease of immunoglobulins and B cells, especially class-switched memory B cells, with normal T and NK cell counts. Analysis of bone marrow of one patient revealed a reduced immature B cell fraction compared with controls. Additional investigations showed that both PLCG2 variants activate the NLRP3-inflammasome through the alternative pathway instead of the canonical pathway. Collectively, the evidences here shown expand APLAID diversity toward more severe phenotypes than previously reported including dominantly inherited agammaglobulinemia, add novel data about its genetic basis, and implicate the alternative NLRP3-inflammasome activation pathway in the basis of sterile inflammation.
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http://dx.doi.org/10.1007/s10875-020-00794-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505877PMC
October 2020

Pediatric antimicrobial stewardship in the COVID-19 outbreak.

Infect Control Hosp Epidemiol 2021 05 24;42(5):642-644. Epub 2020 Jun 24.

Infectious Diseases Unit, Department of Pediatrics, Sant Joan de Déu Hospital, Barcelona, Spain.

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http://dx.doi.org/10.1017/ice.2020.312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338437PMC
May 2021

Benefits of a Pediatric Antimicrobial Stewardship Program in Antimicrobial Use and Quality of Prescriptions in a Referral Children's Hospital.

J Pediatr 2020 10 6;225:222-230.e1. Epub 2020 Jun 6.

Infectious Diseases and Systemic Inflammatory Response in Pediatrics, Infectious Diseases Unit, Department of Pediatrics, Sant Joan de Déu Hospital Research Foundation, Barcelona, Spain; Center for Biomedical Network Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Pediatrics, University of Barcelona, Barcelona, Spain; Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain. Electronic address:

Objectives: To evaluate the results of the first 24 months of a postprescription review with feedback-based antimicrobial stewardship program in a European referral children's hospital.

Study Design: We performed a pre-post study comparing antimicrobial use between the control (2015-2016) and the intervention periods (2017-2018) expressed in days of therapy/100 days present. Quality of prescriptions was evaluated by quarterly cross-sectional point-prevalence surveys. Length of stay, readmission rates, in-hospital mortality rates, cost of systemic antimicrobial agents, and antimicrobial resistance rates were included as complementary outcomes.

Results: Total antimicrobial use and antibacterial use significantly decreased during the intervention period (P = .002 and P = .001 respectively), and total antifungal use remained stable. A significant decline in parenteral antimicrobial use was also observed (P < .001). In 8 quarterly point-prevalence surveys (938 prescriptions evaluated), the mean prevalence of use of any antimicrobial among inpatients was 39%. An increasing trend in the rate of optimal prescriptions was observed after the first point-prevalence survey (P = .0898). Nonoptimal prescriptions were more common in surgical than in medical departments, in antibacterial prescriptions with prophylactic intention, and in empirical more than in targeted treatments. No significant differences were observed in terms of mortality or readmission rates. Only minor changes in antimicrobial resistance rates were noted.

Conclusions: Our antimicrobial stewardship program safely decreased antimicrobial use and expenditure, and a trend toward improvement in quality of prescription was also observed.
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http://dx.doi.org/10.1016/j.jpeds.2020.06.008DOI Listing
October 2020

Response to direct-acting antivirals for hepatitis C treatment in vertically HIV/HCV co-infected patients.

J Viral Hepat 2020 09 22;27(9):955-958. Epub 2020 May 22.

Hospital General Universitario Gregorio Marañón and Gregorio Marañón Research Institute (IiSGM), Madrid, Spain.

Direct-acting antivirals (DAAs) for HCV treatment have improved tolerance and efficacy among adults, but experience in vertical transmission is scarce. In our vertically HIV/HCV co-infected youth cohort of 58 patients, DAA achieved excellent rates of cure among naïve and pretreated individuals. Treating vertically infected seems important as 29.6% displayed advanced fibrosis at treatment initiation.
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http://dx.doi.org/10.1111/jvh.13308DOI Listing
September 2020

Safety and Efficacy of Fidaxomicin and Vancomycin in Children and Adolescents with Clostridioides (Clostridium) difficile Infection: A Phase 3, Multicenter, Randomized, Single-blind Clinical Trial (SUNSHINE).

Clin Infect Dis 2020 12;71(10):2581-2588

Astellas Pharma B.V., Leiden, the Netherlands.

Background: Fidaxomicin, a narrow-spectrum antibiotic approved for Clostridioides (Clostridium) difficile infection (CDI) in adults, is associated with lower rates of recurrence than vancomycin; however, pediatric data are limited. This multicenter, investigator-blind, phase 3, parallel-group trial assessed the safety and efficacy of fidaxomicin in children.

Methods: Patients aged <18 years with confirmed CDI were randomized 2:1 to 10 days of treatment with fidaxomicin (suspension or tablets, twice daily) or vancomycin (suspension or tablets, 4 times daily). Safety assessments included treatment-emergent adverse events. The primary efficacy end point was confirmed clinical response (CCR), 2 days after the end of treatment (EOT). Secondary end points included global cure (GC; CCR without CDI recurrence) 30 days after EOT (end of study; EOS). Plasma and stool concentrations of fidaxomicin and its active metabolite OP-1118 were measured.

Results: Of 148 patients randomized, 142 were treated (30 <2 years old). The proportion of participants with treatment-emergent adverse events was similar with fidaxomicin (73.5%) and vancomycin (75.0%). Of 3 deaths in the fidaxomicin arm during the study, none were CDI or treatment related. The rate of CCR at 2 days after EOT was 77.6% (76 of 98 patients) with fidaxomicin and 70.5% (31 of 44) with vancomycin, whereas the rate of GC at EOS was significantly higher in participants receiving fidaxomicin (68.4% vs 50.0%; adjusted treatment difference, 18.8%; 95% confidence interval, 1.5%-35.3%). Systemic absorption of fidaxomicin and OP-1118 was minimal, and stool concentrations were high.

Conclusions: Compared with vancomycin, fidaxomicin was well tolerated and demonstrated significantly higher rates of GC in children and adolescents with CDI.

Clinical Trials Registration: NCT02218372.
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http://dx.doi.org/10.1093/cid/ciz1149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744996PMC
December 2020

Growth Patterns in Children With Congenital Cytomegalovirus Infection.

Pediatr Infect Dis J 2019 12;38(12):1230-1235

Fundación para la Investigación Biomédica del Hospital 12 de Octubre, Pediatric Infectious Diseases Research Group, Madrid, Spain.

Background: Congenital cytomegalovirus infection (CMVc) affects 0.7%-6% of recent births. Among its clinical manifestations are low weight and length at birth.

Objective: Describe the growth patterns of children with CMVc in their early years.

Methods: Observational, multicenter study of patients with CMVc. Anthropometric data were collected during the first 2 years of life and compared with World Health Organization standards.

Results: Anthropometric characteristics of 383 children with CMVc were studied, of which 198 (51%) were symptomatic at birth. At birth, 9% were small for gestational age (SGA) in terms of their weight and length and 17% had microcephaly. At 24 ± 3 months, 10% had a weight and length ≤2 SD, and 13% a head circumference ≤2 SD. Of those who were SGA at birth, at 24 ± 3 months >20% remained at ≤2 SD of their weight and length. Conversely, 75% of children with low weight or length at 24 ± 3 had not been SGA at birth. 20% of infants with microcephaly at birth remained with microcephaly, and 10% of those without microcephaly developed it at 24 ± 3 months. The average growth rate in length and weight was normal. Patients who were symptomatic at birth, premature and with motor and neurocognitive impairment had a significantly higher risk of low weight and length at 24 ± 3 months.

Conclusion: Around 10% of children with CMVc are at ≤2 SD in weight, length and head circumference at 24 ± 3 months. The lack of adequate growth is associated with symptoms at birth, prematurity and motor and neurocognitive impairment. Growth impairment could be incorporated into the symptomatic spectrum of CMVc.
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http://dx.doi.org/10.1097/INF.0000000000002483DOI Listing
December 2019

Impact of Baseline Tuberculin Skin Test and Isoniazid Chemoprophylaxis on Subsequent Quantiferon-TB Gold In-Tube Performance in Young Children Assessed After Tuberculosis Contact in Catalonia.

Pediatr Infect Dis J 2020 02;39(2):e22-e25

From the Malalties Infeccioses i Resposta Inflamatòria Sistèmica en Pediatria, Unitat d´Infeccions, Servei de Pediatria, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain.

We investigated the impact of baseline tuberculin skin tests (TSTs) and preventive isoniazid chemoprophylaxis on subsequent QuantiFERON-TB Gold In-Tube (QFT-GIT) assays performed after a 10- to 12-week window period in 114 children <5 years of age. Previous TSTs and chemoprophylaxis had no impact on the magnitude of subsequent antigen-induced responses in QFT-GIT. Furthermore, previous TSTs did not induce conversion from a negative to a positive QFT-GIT result.
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http://dx.doi.org/10.1097/INF.0000000000002517DOI Listing
February 2020

Sociodemographic changes and trends in the rates of new perinatal HIV diagnoses and transmission in Spain from 1997 to 2015.

PLoS One 2019 24;14(10):e0223536. Epub 2019 Oct 24.

Sección de Enfermedades Infecciosas, Servicio de Pediatría, Hospital General Universitario Gregorio Marañón and Instituto de Investigación Sanitaria Gregorio Marañón, Medical School, Universidad Complutense de Madrid, Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain.

Background: There are not enough nationwide studies on perinatal HIV transmission in connection with a combination of antiretroviral treatments in Spain. Our objectives were to study sociodemographic changes and trends in the rates of HIV diagnoses and perinatal transmission in Spain from 1997 to 2015.

Methods: A retrospective study using data from Spanish Paediatric HIV Network (CoRISpe) and Spanish Minimum Basic Data Set (MDBS) was performed. HIV- diagnosed children between 1997 and 2015 were selected. Sociodemographic, clinical and immunovirological data of HIV-infected children and their mothers were studied in four calendar periods (P1: 1997-2000; P2: 2001-2005; P3: 2006-2010; P4: 2011-2015). Rates of perinatal HIV diagnoses and transmission from 1997 to 2015 were calculated.

Results: A total of 532 HIV-infected children were included in this study. Of these children, 406 were Spanish (76.3%) and 126 immigrants (23.7%). A decrease in the number of HIV diagnoses, 203 (38.2%) children in the first (P1), 149 (28%) in the second (P2), 130 (24.4%) in the third (P3) and 50 (9.4%) in the fourth (P4) calendar periods was studied. The same decrease in the Spanish HIV-infected children (P1, 174 (46.6%), P2, 115 (30.8%), P3, 65 (17.4%) and P4, 19 (5.1%)) was monitored. However, an increase in the number of HIV diagnoses by sexual contact (P1: 0%; P2: 1.3%; P3: 4.6%; P4: 16%) was observed. The rates of new perinatal HIV diagnoses and perinatal transmission in Spanish children decreased from 0.167 to 0.005 per 100,000 inhabitants and 11.4% to 0.4% between 1997 and 2015, respectively.

Conclusions: A decline of perinatal HIV diagnoses and transmission was observed. However, an increase of teen-agers HIV diagnoses with sexual infection was studied. Public awareness campaigns directed to teen-agers are advisable to prevent HIV infection by sexual contact.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223536PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812742PMC
March 2020

Longitudinal evolution of vertically HIV/HCV-co-infected vs HCV-mono-infected children.

J Viral Hepat 2020 01 30;27(1):61-67. Epub 2019 Oct 30.

TRaslational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain.

HIV co-infection has been suggested to play a deleterious role on the pathogenesis of liver fibrosis among vertically HCV-infected children. The aim of this study was to describe the longitudinal evolution of vertically acquired HIV/HCV co-infection in youths, in comparison with HCV infection alone. This was a retrospective, multicentre study including vertically HIV/HCV-co-infected patients and age- and sex-matched vertically HCV-mono-infected patients. Progression to advanced liver fibrosis, defined as F3 or more by elastography or METAVIR biopsy staging, and response to treatment were compared by means of univariate and multivariate regression analyses and Cox regression models. Sixty-seven co-infected patients were compared with 67 matched HCV-mono-infected patients. No progression to advanced liver disease was observed during the first decade. At a median age of 20.0 [19.0, 22.0] years, 26.7% co-infected vs 20% mono-infected had progressed to advanced fibrosis (P = .617). Peg-IFN/RBV for HCV treatment was given to 37.9% vs 86.6% (P-value < .001). At treatment initiation, co-infected patients were older (16.9 ± 4.1 vs 11.7 ± 4.5 years, P < .001), and 47.1% vs 7.1% showed advanced fibrosis (P < .003), with no differences in hard-to-treat genotype distribution. Sustained viral response was comparable between groups (43.5% vs 44.0%, P = .122). In vertically HIV/HCV-co-infected patients, the progression to liver fibrosis was rare during childhood. At the end of adolescence, over 25% of patients displayed advanced liver disease. Response to Peg-IFN/RBV was poor and comparable in both groups, supporting the need for fast access to early treatment with direct-acting antivirals against HCV for vertically co-infected patients.
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http://dx.doi.org/10.1111/jvh.13206DOI Listing
January 2020

Cerebrospinal Fluid Neopterin in Children With Enterovirus-Related Brainstem Encephalitis.

Pediatr Neurol 2019 07 7;96:70-73. Epub 2019 Feb 7.

Department of Pediatrics, Hospital Sant Joan de Deu (University of Barcelona), Barcelona, Spain; Pediatric Infectious Diseases Research Group, Institut de Recerca Sant Joan de Deu, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Electronic address:

Background: Enterovirus-A71 causes outbreaks of brainstem encephalitis, ranging from self-limited disease to acute flaccid paralysis. The aim of this study was to assess the role of cerebrospinal fluid (CSF) neopterin as a biomarker of disease severity in children with enterovirus-related brainstem encephalitis.

Methods: A descriptive, prospective cohort study was conducted from April 2016 to March 2017 in a tertiary hospital. Pediatric patients with a diagnosis of brainstem encephalitis with or without myelitis due to enterovirus infection were enrolled. The final study group comprised a convenience sample including all patients with sufficient CSF volume for neopterin determination. The major variables considered in estimating the severity were the diagnosis of encephalomyelitis, the presence of lesions and extensive lesions on brain and spinal magnetic resonance imaging (MRI), hospital stay length greater than seven days, and sequelae at day 30.

Results: Of 60 patients, CSF neopterin could be measured in 36. Median age was 26 months (interquartile range: 19 to 32). Thirty-three were diagnosed with brainstem encephalitis and three with encephalomyelitis. Enterovirus-A71 was the only identified genotype (25 of 25). CSF neopterin levels were elevated (>61 nmol/L) in 33 of 36 (92%), with a median of 347 nmol/L (interquartile range: 204 to 525). CSF neopterin was useful to distinguish patients with lesions on MRI (area under the receiver operating characteristic curve = 0.76; P = 0.02) and extensive lesions (area under the receiver operating characteristic curve = 0.76; P = 0.04).

Conclusions: This study suggests an association between CSF neopterin levels and the presence of inflammatory lesions on MRI.
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http://dx.doi.org/10.1016/j.pediatrneurol.2019.01.024DOI Listing
July 2019

Effect of Hepatitis C Virus Coinfection on the Progression of Vertically Acquired Human Immunodeficiency Virus Infection During Childhood and Adolescence.

J Pediatric Infect Dis Soc 2020 Apr;9(2):232-235

Departments of Pediatric Infectious Diseases, University Hospital Gregorio Marañón and Gregorio Marañón Research Institute (IiSGM), Madrid.

Data for a total of 57 patients vertically coinfected with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) and 365 HIV-monoinfected patients were compared until their transition to adult care. No differences regarding the dynamics of CD4 and/or CD8 T-cell counts during childhood were found. The coexistence of HCV does not increase the risk of disease progression in vertically HIV-infected patients.
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http://dx.doi.org/10.1093/jpids/piz008DOI Listing
April 2020

Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With or Without Ribavirin for Adolescents With HCV Genotype 1 or 4.

Hepatol Commun 2018 Nov 5;2(11):1311-1319. Epub 2018 Oct 5.

Department of Pediatrics University of California San Francisco San Francisco CA.

In adults, treatment of hepatitis C virus (HCV) infection with ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) with or without dasabuvir (DSV) and ±ribavirin (RBV) results in high rates of sustained virologic response (SVR). However, these regimens have not been investigated in adolescents. This ongoing, open-label, phase 2/3 study evaluated the pharmacokinetics, safety, and efficacy of OBV/PTV/r+DSV±RBV treatment for 12 weeks in adolescents infected with HCV genotype (GT) 1 without cirrhosis (part 1) and the safety and efficacy of OBV/PTV/r±DSV±RBV treatment for 12 or 24 weeks in adolescents infected with GT1 or GT4 without cirrhosis or with compensated cirrhosis (parts 1 and 2). Patients were 12-17 years of age and treatment naive or interferon experienced. Treatment regimens were based on HCV GT and cirrhosis status. Endpoints were SVR at posttreatment week 12 (SVR12), adverse events (AEs), and pharmacokinetic parameters. Thirty-eight adolescents were enrolled, 66% were female patients, and 76% were White; 42%, 40%, and 18% of patients had HCV GT1a, GT1b, and GT4 infections, respectively. Median age was 15 years (range, 12-17 years), and 1 patient had cirrhosis. The SVR12 rate was 100% (38/38; 95% confidence interval [CI], 90.8%-100%). No treatment-emergent grade 3 or 4 laboratory abnormalities were reported. No serious AEs occurred on treatment, and no AEs led to study drug discontinuation. The most common AEs were headache (21%), fatigue (18%), nasopharyngitis (13%), pruritus (13%), and upper respiratory tract infection (11%). Intensive pharmacokinetic results showed OBV, PTV, DSV, and ritonavir drug exposures were comparable to those seen in adults. Treatment with OBV/PTV/r±DSV±RBV was well tolerated and highly efficacious in adolescents with HCV GT1 or GT4 infection.
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http://dx.doi.org/10.1002/hep4.1250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211326PMC
November 2018

Performance of Tuberculin Skin Tests and Interferon-γ Release Assays in Children Younger Than 5 Years.

Pediatr Infect Dis J 2018 12;37(12):1235-1241

From the Malalties Infeccioses i Resposta Inflamatòria Sistèmica en Pediatria, Unitat d´Infeccions, Servei de Pediatria, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain.

Background: Available data to assess the optimal diagnostic approach in infants and preschool children at risk of tuberculosis (TB) are limited.

Methods: We conducted a prospective observational study in children younger than 5 years undergoing assessment with both tuberculin skin tests (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT) assays at 2 tertiary TB units in Barcelona, Spain.

Results: A total of 383 children were included. One of 304 participants considered uninfected developed active TB during follow-up {median [interquartile range (IQR)]: 47 [30; 48] months}, compared with none of 40 participants with latent TB infection [follow-up since completion of anti-TB treatment: 42 (32; 45) months]. Overall test agreement between TST and QFT-GIT was moderate (κ = 0.551), but very good in children screened after TB contact (κ = 0.801) and in Bacillus Calmette-Guérin (BCG)-unvaccinated children (κ = 0.816). Discordant results (16.8%, all TST+/QFT-GIT-) were mainly observed in new-entrant screening and in BCG-vaccinated children. Children with indeterminate QFT-GIT results were on average younger than those with determinate results (median age: 12 vs. 30 months; P < 0.001). The sensitivity of TSTs and QFT-GIT assays in children with confirmed active TB was 100% (95% confidence interval: 79.4%-100%) and 93.7% (95% confidence interval: 69.8%-99.8%), respectively. In patients with latent TB infection or active TB, there was no correlation between age and antigen-stimulated interferon-γ responses (r = -0.044; P = 0.714).

Conclusions: In young BCG-unvaccinated children with recent TB contact, a dual testing strategy using TST and QFT-GIT in parallel may not be necessary. However, TST+/QFT-GIT- discordance is common, and it remains uncertain if this constellation indicates TB infection or not. In active TB, QFT-GIT assays do not perform better than TSTs.
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http://dx.doi.org/10.1097/INF.0000000000002015DOI Listing
December 2018

Early and Highly Suppressive Antiretroviral Therapy Are Main Factors Associated With Low Viral Reservoir in European Perinatally HIV-Infected Children.

J Acquir Immune Defic Syndr 2018 10;79(2):269-276

Department of Pediatrics, Hospital 12 de Octubre, Fundación para la Investigación Biomédica del Hospital Universitario 12 de Octubre, Madrid, Spain.

Background: Future strategies aiming to achieve HIV-1 remission are likely to target individuals with small reservoir size.

Setting: We retrospectively investigated factors associated with HIV-1 DNA levels in European, perinatally HIV-infected children starting antiretroviral therapy (ART) <6 months of age.

Methods: Total HIV-1 DNA was measured from 51 long-term suppressed children aged 6.3 years (median) after initial viral suppression. Factors associated with log10 total HIV-1 DNA were analyzed using linear regression.

Results: At ART initiation, children were aged median [IQR] 2.3 [1.2-4.1] months, CD4% 37 [24-45] %, CD8% 28 [18-36] %, log10 plasma viral load (VL) 5.4 [4.4-5.9] copies per milliliter. Time to viral suppression was 7.98 [4.6-19.3] months. After suppression, 13 (25%) children had suboptimal response [≥2 consecutive VL 50-400 followed by VL <50] and/or experienced periods of virological failure [≥2 consecutive VL ≥400 followed by VL <50]. Median total HIV-1 DNA was 43 [6195] copies/10 PBMC. Younger age at therapy initiation was associated with lower total HIV-1 DNA (adjusted coefficient [AC] 0.12 per month older, P = 0.0091), with a month increase in age at ART start being associated with a 13% increase in HIV DNA. Similarly, a higher proportion of time spent virally suppressed (AC 0.10 per 10% higher, P = 0.0022) and the absence of viral failure/suboptimal response (AC 0.34 for those with fail/suboptimal response, P = 0.0483) were associated with lower total HIV-1 DNA.

Conclusions: Early ART initiation and a higher proportion of time suppressed are linked with lower total HIV-1 DNA. Early ART start and improving adherence in perinatally HIV-1-infected children minimize the size of viral reservoir.
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http://dx.doi.org/10.1097/QAI.0000000000001789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173292PMC
October 2018

Is Polymerase Chain Reaction in Neonatal Dried Blood Spots Reliable for the Diagnosis of Congenital Cytomegalovirus Infection?

Pediatr Infect Dis J 2019 05;38(5):520-524

Servicio de Pediatría, Hospital Joan XIII, Tarragona, Spain.

Background: Detection of cytomegalovirus (CMV) DNA by real-time polymerase chain reaction (rt-PCR) in dried blood spots (DBSs) collected for newborn screening has been assessed for retrospective diagnosis of congenital CMV (cCMV) infection, with variable results (sensitivities ranging from 34% to 100%). We aimed to assess the accuracy of this technique in Spain in a large patient series.

Methods: Ambispective, multicenter study including patients with confirmed cCMV from the Spanish Registry of cCMV patients. cCMV was established on the presence of CMV DNA in any body fluid, by positive culture findings or by molecular techniques during the first 2 weeks of life. Children in whom cCMV had been excluded were used as negative controls. Neonatal DBS samples were collected from both groups. The presence of CMV DNA was assessed by rt-PCR (RealStar CMV, Altona, Germany) in a central laboratory.

Results: One-hundred three patients and 81 controls from 10 hospitals were included. The performance of CMV DNA determination in DBS for the diagnosis of cCMV was as follows (95% confidence interval): sensitivity 0.56 (0.47-0.65), specificity 0.98 (0.91-0.99), positive likelihood ratio 22.81 (5.74-90.58) and negative likelihood ratio 0.45 (0.36-0.56). Sensitivity increased with the birth viral load (bVL) log category. In cCMV patients, lower bVL was the single variable associated with a negative DBS rt-PCR result (P = 0.017).

Conclusions: The sensitivity of CMV rt-PCR in DBS in our series was low and correlated with the bVL. Thus, a negative DBS result would not rule out cCMV infection, especially in patients with a low viremia level at birth.
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http://dx.doi.org/10.1097/INF.0000000000002144DOI Listing
May 2019
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