Enterovirus D68 in Hospitalized Children, Barcelona, Spain, 2014-2021.

To determine molecular epidemiology and clinical features of enterovirus D68 (EV-D68) infections, we reviewed EV-D68-associated respiratory cases at a hospital in Barcelona, Spain, during 2014-2021. Respiratory samples were collected from hospitalized patients or outpatients with symptoms of acute respiratory tract infection or suggestive of enterovirus infection. Enterovirus detection was performed by real-time multiplex reverse transcription PCR and characterization by phylogenetic analysis of the partial viral protein 1 coding region sequences. From 184 patients with EV-D68 infection, circulating subclades were B3 (80%), D1 (17%), B2 (1%), and A (<1%); clade proportions shifted over time. EV-D68 was detected mostly in children (86%) and biennially (2016, 2018, 2021). In patients <16 years of age, the most common sign/symptom was lower respiratory tract infection, for which 11.8% required pediatric intensive care unit admission and 2.3% required invasive mechanical ventilation; neurologic complications developed in 1. The potential neurotropism indicates that enterovirus surveillance should be mandatory.

Pertactin-Deficient Bordetella pertussis with Unusual Mechanism of Pertactin Disruption, Spain, 1986-2018.

Bordetella pertussis not expressing pertactin has increased in countries using acellular pertussis vaccines (ACV). The deficiency is mostly caused by pertactin gene disruption by IS481. To assess the effect of the transition from whole-cell vaccine to ACV on the emergence of B. pertussis not expressing pertactin in Spain, we studied 342 isolates collected during 1986-2018. We identified 93 pertactin-deficient isolates. All were detected after introduction of ACV and represented 38% of isolates collected during the ACV period; 58.1% belonged to a genetic cluster of isolates carrying the unusual prn::del(-292, 1340) mutation. Pertactin inactivation by IS481 insertion was identified in 23.7% of pertactin-deficient isolates, arising independently multiple times and in different phylogenetic branches. Our findings support the emergence and dissemination of a cluster of B. pertussis with an infrequent mechanism of pertactin disruption in Spain, probably resulting from introduction of ACV.

Candida species biotypes and polyclonality of potentially virulent Candida albicans isolated from oral cavity of patients with orofacial clefts.

OBJECTIVES: This study evaluated the incidence of Candida species, and the genetic diversity and virulence of C. albicans of the oral cavity from patients with cleft lip and palate (CLP). MATERIALS AND METHODS: Oral samples were investigated by microbiological and species-specific PCR methods. The genetic diversity of C. albicans was established using isoenzyme markers, Nei's statistics, and clustering analysis. Hydrolytic enzymes (SAPs and PLs) were analyzed in vitro. RESULTS: Oral colonization by Candida species was observed in 29 patients with CLP (65.9%), and C. albicans was highly prevalent. SAP and PL activities were observed in 100% and 51.9% of isolates, respectively. High genetic diversity and patterns of monoclonal and polyclonal oral colonization by C. albicans were observed among patients with CLP. Two major polymorphic taxa (A and B) and other minor polymorphic taxa (C to J) were identified. Only one of the 16 clusters (taxon A) harbored strains from patients with and without CLP, whereas other clusters harbored strains exclusively from CLP patients. CONCLUSIONS: The anatomical conditions of the oral cavity of patients with CLP contribute to the high incidence of Candida species (C. albicans, C. krusei, C. tropicalis, and/or Candida spp.). Data suggest high genetic diversity of potentially virulent C. albicans strains in the oral cavity of CLP patients. CLINICAL RELEVANCE: Microbiological niches in orofacial clefts can contribute to the emergence of a relative clinical genotypic identity of C. albicans. However, orofacial rehabilitation centers can contribute to the direct and indirect sources of transmission and propagation of Candida species.

Descemet's membrane injury and regeneration, and posterior corneal fibrosis, in rabbits.

The purpose of this investigation was to study Descemet's membrane and corneal endothelial regeneration, myofibroblast generation and disappearance, and TGF beta-1 localization after Descemet's membrane-endothelial excision (Descemetorhexis) in rabbits. Thirty-six rabbits had 8 mm Descemetorhexis and standardized slit lamp photos at 1, 2 and 4 days, 1, 2 and 4 weeks, and 2, 4 and 6 months, as well as multiplex IHC for stromal cell markers keratocan, vimentin, and alpha-smooth muscle actin (SMA); basement membrane (BM) components perlecan, nidogen-1, laminin alpha-5, and collagen type IV; and corneal endothelial marker Na,K-ATPase ß1, and TGF beta-1, with ImageJ quantitation. Stromal transparency increased from the periphery beginning at two months after injury and progressed into the central cornea by six months. At six months, central transparency was primarily limited by persistent mid-stromal neovascularization. Stromal myofibroblast zone thickness in the posterior stroma peaked at one month after injury, and then progressively decreased until to six months when few myofibroblasts remained. The regeneration of a laminin alpha-5 and nidogen-1 Descemet's membrane "railroad track" structure was accompanied by corneal endothelial closure and stromal cell production of BM components in corneas from four to six months after injury. TGF beta-1 deposition at the posterior corneal surface from the aqueous humor peaked at one day after Descemetorhexis and diminished even before regeneration of the endothelium and Descemet's membrane. This decrease was associated with collagen type IV protein production by corneal fibroblasts, and possibly myofibroblasts, in the posterior stroma. Descemet's membrane and the corneal endothelium regenerated in the rabbit cornea by six months after eight mm Descemetorhexis. Real-time quantitative RT-PCR experiments in vitro with marker-verified rabbit corneal cells found that 5 ng/ml or 10 ng/ml TGF beta-1 upregulated col4a1 or col4a2 mRNA expression after 6 h or 12 h of exposure in corneal fibroblasts, but not in myofibroblasts. Stromal cells produced large amounts of collagen type IV that likely decreased TGF beta-1 penetration into the stroma and facilitated the resolution of myofibroblast-generated fibrosis.

TGFß1 and TGFß2 proteins in corneas with and without stromal fibrosis: Delayed regeneration of apical epithelial growth factor barrier and the epithelial basement membrane in corneas with stromal fibrosis.

The purpose of this study was to investigate the expression and localization of transforming growth factor (TGF) ß1 and TGFß2 in rabbit corneas that healed with and without stromal fibrosis, and to further study defective perlecan incorporation in the epithelial basement membrane (EBM) in corneas with scarring fibrosis. A total of 120 female rabbits had no surgery, -4.5D PRK, or -9D PRK. Immunohistochemistry (IHC) was performed at time points from unwounded to eight weeks after surgery, with four corneas at each time point in each group. Multiplex IHC was performed for TGFß1 or TGFß2, with Image-J quantitation, and keratocan, vimentin, alpha-smooth muscle actin (SMA), perlecan, laminin-alpha 5, nidogen-1 or CD11b. Corneas at the four-week peak for myofibroblast and fibrosis development were evaluated using Imaris 3D analysis. Delayed regeneration of both an apical epithelial growth factor barrier and EBM barrier function, including defective EBM perlecan incorporation, was greater in high injury -9D PRK corneas compared to -4.5D PRK corneas without fibrosis. Defective apical epithelial growth factor barrier and EBM allowed epithelial and tear TGFß1 and tear TGFß2 to enter the corneal stroma to drive myofibroblast generation in the anterior stroma from vimentin-positive corneal fibroblasts, and likely fibrocytes. Vimentin-positive cells and unidentified vimentin-negative, CD11b-negative cells also produce TGFß1 and/or TGFß2 in the stroma in some corneas. TGFß1 and TGFß2 were at higher levels in the anterior stroma in the weeks preceding myofibroblast development in the -9D group. All -9D corneas (beginning two to three weeks after surgery), and four -4.5D PRK corneas developed significant SMA + myofibroblasts and stromal fibrosis. Both the apical epithelial growth factor barrier and/or EBM barrier functions tended to regenerate weeks earlier in -4.5D PRK corneas without fibrosis, compared to -4.5D or -9D PRK corneas with fibrosis. SMA-positive myofibroblasts were markedly reduced in most corneas by eight weeks after surgery. The apical epithelial growth factor barrier and EBM barrier limit TGFß1 and TGFß2 entry into the corneal stroma to modulate corneal fibroblast and myofibroblast development associated with scarring stromal fibrosis. Delayed regeneration of these barriers in corneas with more severe injuries promotes myofibroblast development, prolongs myofibroblast viability and triggers stromal scarring fibrosis.

Descemet's membrane development, structure, function and regeneration.

Basement membranes are layers of extracellular matrix which anchor the epithelium or endothelium to connective tissues in most organs. Descemet's membrane- which is the basement membrane for the corneal endothelium- is a dense, thick, relatively transparent and cell-free matrix that separates the posterior corneal stroma from the underlying endothelium. It was historically named Descemet's membrane after Jean Descemet, a French physician, but it is also known as the posterior limiting elastic lamina, lamina elastica posterior, and membrane of Demours. Normal Descemet's membrane ultrastructure in humans has been shown to consist of an interfacial matrix that attaches to the overlying corneal stroma, an anterior banded layer and a posterior non-banded layer-upon which corneal endothelial cells attach. These layers have been shown to have unique composition and morphology, and to contribute to corneal homeostasis and clarity, participate in the control of corneal hydration and to modulate TGF-ß-induced posterior corneal fibrosis. Pathophysiological alterations of Descemet's membrane are noted in ocular diseases such as Fuchs' dystrophy, bullous keratopathy, keratoconus, primary congenital glaucoma (Haab's striae), as well as in systemic conditions. Unrepaired extensive damage to Descemet's membrane results in severe corneal opacity and vision loss due to stromal fibrosis, which may require penetrating keratoplasty to restore corneal transparency. The purpose of this article is to highlight the current understanding of Descemet's membrane structure, function and potential for regeneration.

The concepts of evidence-based periodontal plastic surgery: Application of the principles of evidence-based dentistry for the treatment of recession-type defects.

The decision-making process for the treatment of recession-type defects is based on translation of the outcomes from randomized controlled trials and systematic reviews to clinical practice. Such an approach is capable of assisting researchers, clinicians, and patients to understand the mechanisms and effects of the treatment of different root-coverage procedures, as well as turning treatment options into usable and predictable tools to be applied in dental practice. This review explores: (a) the aspects related to the etiology of gingival recession; (b) the history of periodontal plastic surgery procedures used to achieve root coverage; (c) the main findings, implications of research, and practice of root-coverage procedures described from the current base of systematic reviews; (d) the role of the evidence produced in Latin American research centers; and (e) the outcomes of an individual patient data meta-analysis of randomized controlled trials evaluating the role of root coverage and restorative procedures in achieving complete root coverage of noncarious cervical lesions. The findings of the current base of evidence clearly indicate that all of the main periodontal plastic surgery procedures lead to improvements in initial clinical parameters, but subepithelial connective tissue grafts, either alone or associated with coronally advanced flaps, result in superior complete root coverage, long-term stability, and greater increase of keratinized tissue. Nonetheless, coronally advanced flaps, either associated with biomaterials (acellular dermal matrix grafts, enamel derivative proteins and xenogeneic collagen matrix) or used alone, provide satisfactory results and are suitable for use as secondary/alternative procedures to subepithelial connective tissue grafts.

Conversion from twice-daily to once-daily tacrolimus formulation in pediatric liver transplant recipients - a long-term prospective study.

To assess the safety and efficacy of conversion from twice-daily tacrolimus to once-daily tacrolimus in pediatric liver transplant recipients. Conversion from twice-daily to once-daily tacrolimus was made in stable pediatric liver transplant recipients. Doses and serum levels of tacrolimus, liver, and renal function were recorded on the day before the conversion and at days 5, 30, 90, and 180 postconversion. Patients were controlled every 2-3 months thereafter. Fifty-five patients were enrolled in the study. The mean age at conversion was 10.2 ± 3.6 years. The mean tacrolimus trough level was 4.7 ± 1.9 ng/dl preconversion, followed by a significant decline to 4.2 ± 1.7 30 days after the switch (P < 0.004). Mean daily tacrolimus dose was 0.09 ± 0.046 mg/Kg preconversion with a significant increase to 0.11 ± 0.060 3 months postconversion (P < 0.001). Fifteen patients with calculated glomerular filtration rate between 60 to 80 ml/min/m2 preconversion showed a significant improvement one and 3 years after the switch (73 ± 4.1, 83 ± 4.3 and 90.3 ± 7.3 ml/min/m2 , respectively (P < 0.001). The mean follow-up was 5.2 ± 2.4 years. Conversion to once-daily tacrolimus is safe and effective in a cohort of stable pediatric liver transplant patients.

Successful long-term outcome of pediatric liver-kidney transplantation: a single-center study.

INTRODUCTION: Liver-kidney transplantation is a rare procedure in children, with just ten to 30 cases performed annually worldwide. The main indications are autosomal recessive polycystic liver-kidney disease and primary hyperoxaluria. This study aimed to report outcomes of liver-kidney transplantation in a cohort of pediatric patients. METHODS: We retrospectively analyzed all pediatric liver-kidney transplantations performed in our center between September 2000 and August 2015. Patient data were obtained by reviewing inpatient and outpatient medical records and our transplant database. RESULTS: A total of 14 liver-kidney transplants were performed during the study period, with a median patient age and weight at transplant of 144.4 months (131.0-147.7) and 27.3 kg (12.0-45.1), respectively. The indications for liver-kidney transplants were autosomal recessive polycystic liver-kidney disease (8/14), primary hyperoxaluria -1 (5/14), and idiopathic portal hypertension with end-stage renal disease (1/14). Median time on waiting list was 8.5 months (5.7-17.3). All but two liver-kidney transplants were performed simultaneously. Patients with primary hyperoxaluria-1 tended to present a delayed recovery of renal function compared with patients transplanted for other indications (62.5 vs 6.5 days, respectively, P 0.076). Patients with liver-kidney transplants tended to present a lower risk of acute kidney rejection than patients transplanted with an isolated kidney transplant (7.2% vs 32.7%, respectively; P < 0.07). Patient and graft survival at 1, 3, and 5 years were 100%, 91.7%, 91.7%, and 91.7%, 83.3%, 83.3%, respectively. No other grafts were lost. CONCLUSION: Long-term results of liver-kidney transplants in children are encouraging, being comparable with those obtained in isolated liver transplantation.

Emergence of Bordetella holmesii as a Causative Agent of Whooping Cough, Barcelona, Spain.

We describe the detection of Bordetella holmesii as a cause of whooping cough in Spain. Prevalence was 3.9% in 2015, doubling to 8.8% in 2016. This emergence raises concern regarding the contribution of B. holmesii to the reemergence of whooping cough and the effectiveness of the pertussis vaccine.

IgM+IgD+CD27+ B cells are markedly reduced in IRAK-4-, MyD88-, and TIRAP- but not UNC-93B-deficient patients.

We studied the distribution of peripheral B-cell subsets in patients deficient for key factors of the TLR-signaling pathways (MyD88, TIRAP/MAL, IL-1 receptor-associated kinase 4 [IRAK-4], TLR3, UNC-93B, TRIF). All TLRs, except TLR3, which signals through the TRIF adaptor, require MyD88 and IRAK-4 to mediate their function. TLR4 and the TLR2 heterodimers (with TLR1, TLR6, and possibly TLR10) require in addition the adaptor TIRAP, whereas UNC-93B is needed for the proper localization of intracellular TLR3, TLR7, TLR8, and TLR9. We found that IgM(+)IgD(+)CD27(+) but not switched B cells were strongly reduced in MyD88-, IRAK-4-, and TIRAP-deficient patients. This defect did not appear to be compensated with age. However, somatic hypermutation of Ig genes and heavy-chain CDR3 size distribution of IgM(+)IgD(+)CD27(+) B cells were not affected in these patients. In contrast, the numbers of IgM(+)IgD(+)CD27(+) B cells were normal in the absence of TLR3, TRIF, and UNC-93B, suggesting that UNC-93B-dependent TLRs, and notably TLR9, are dispensable for the presence of this subset in peripheral blood. Interestingly, TLR10 was found to be expressed at greater levels in IgM(+)IgD(+)CD27(+) compared with switched B cells in healthy patients. Hence, we propose a role for TIRAP-dependent TLRs, possibly TLR10 in particular, in the development and/or maintenance of IgM(+)IgD(+)CD27(+) B cells in humans.

Early exposure of infants to natural rotavirus infection: a review of studies with human rotavirus vaccine RIX4414.

BACKGROUND: Rotaviruses are the leading cause of severe acute gastroenteritis in children aged <5 years worldwide. A live attenuated human rotavirus vaccine, RIX4414 has been developed to reduce the global disease burden associated with rotavirus gastroenteritis. Serum anti-rotavirus immunoglobulin A (IgA) antibody measured in unvaccinated infants during clinical trials of RIX4414 reflects natural rotavirus exposure, and may inform the optimal timing for rotavirus vaccination. METHODS: We reviewed phase II and III randomized, placebo-controlled clinical trials conducted by GlaxoSmithKline Vaccines, Wavre, Belgium between 2000 and 2008 which used the commercial formulation of RIX4414 lyophilized vaccine. We included trials for which demographic data and pre-dose-1 and post-last-dose anti-rotavirus IgA antibody status were available from placebo recipients. RESULTS: Sixteen clinical trials met the inclusion criteria. The studies were conducted across Africa (N = 3), Asia (N = 4), Latin America (N = 4), Europe (N = 4) and North America (N = 1). Overall, 46,398 infants were enrolled and among these, 20,099 received placebo. The mean age at pre-dose-1 time point ranged from 6.4 - 12.2 weeks while the mean age at post-last-dose time point ranged from 13.5 - 19.6 weeks. The anti-RV IgA seropositivity rates at both time points were higher in less developed countries of Africa, Asia and Latin America (pre-dose-1: 2.1%-26.3%; post-last-dose: 6.3%-34.8%) when compared to more developed countries of Asia, Europe and North America (pre-dose-1: 0%-9.4%; post-last-dose: 0%-21.3%), indicating that rotavirus infections occurred at a younger age in these regions. CONCLUSION: Exposure to rotavirus infection occurred early in life among infants in most geographical settings, especially in developing countries. These data emphasize the importance of timely rotavirus vaccination within the Expanded Program on Immunization schedule to maximize protection.

Celiac disease diagnosis: transglutaminase, duodenal biopsy and genetic tests correlations.

Introduction: Celiac disease (CD) is an autoimmune enteropathy triggered by gluten ingestion in genetically susceptible individuals. The haplotypes HLA-DQ2 and DQ8, transglutaminase (TGA) antibodies, and biopsy findings are the main tests performed in the evaluation and CD diagnosis. The objective was to establish possible correlations between transglutaminase levels, genetic markers tests, and qualitative intestinal biopsy findings (modified Marsh classification) at the diagnosis. Methods: A retrospective cohort study. The selection criteria were confirmed CD cases with genetic tests performed. Statistical analysis was done mainly through One-way ANOVA, Kendall's correlation coefficient (T), and linear regression. Results: The study included 112 patients, with a mean age of 6 ± 4 years. All cases were tested to HLA-DQ2, and it was positive in 93%. HLA-DQ8 was tested in 73% of cases and it was positive in 61%. The percentage of negative genetic markers (DQ2/DQ8) was 4.5% for patients tested to both haplotypes. A comparison of DQ2/DQ8 (positive and negative) with clinical findings and tests performed did not identify any differences for most of the parameters analyzed. Cases of type I diabetes presented significant negative expression for DQ2(-); p = 0.05 and positive expression for DQ8(+); p = 0.023. The TGA antibody levels ranged from 18 to 36,745 U/ml. An inverse correlation was found between age and TGA-L level (p = 0.043). In 23% of the cases, the TGA levels were greater than 1,000 U/ml and presented a moderate positive correlation with the atrophy biopsy profile (T = 0.245). Patients with an atrophic biopsy profile (Marsh III) had a moderate positive correlation with growth failure (T = 0.218) but a negative correlation with constipation (T = -0.277). Conclusion: In terms of diagnosis tests for CD, transglutaminase levels and age presented an inverse correlation, with the level decreasing as age increased. A moderately positive correlation was found between mean transglutaminase with intestinal atrophy and growth retardation. The genetic test DQ2 was positive for 93% and negative genetic markers (DQ2/DQ8) represented 4.5% of cases studied.

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.

New Antibiotics for Staphylococcus aureus Infection: An Update from the World Association of Infectious Diseases and Immunological Disorders (WAidid) and the Italian Society of Anti-Infective Therapy (SITA).

Staphylococcus aureus is an extremely virulent pathogen that is capable of quickly evolving and developing antibiotic resistance. To overcome this problem, new antibiotics have been developed. Some of these have been licenced for use in clinical practice, mainly for the treatment of adults with acute skin and soft tissue infections, in addition to both community-acquired pneumonia (CAP) and nosocomial pneumonia (hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia). In this paper, the main characteristics and clinical use of new licenced anti-staphylococcal drugs have been discussed. In vitro studies have demonstrated that some new anti-staphylococcal antibiotics have better antimicrobial activity and, at least in certain cases, more favourable pharmacokinetic properties and higher safety and tolerability than the presently available anti-staphylococcal drugs. This suggests that they may have a potential use in reducing the risk of failure of S. aureus therapy. However, an in-depth analysis of microbiological and clinical studies carried out with these new drugs seems to indicate that further studies need to be conducted before the problem of resistance of S. aureus to the antibiotics available today can be completely solved. Considering the overall available research, the drugs that are active against S. aureus appear to present a great therapeutic opportunity for overcoming resistance to traditional therapy. There are advantages in the pharmacokinetic characteristics of some of these drugs and they have the potential to reduce hospital stays and economic costs associated with their use.

Nirsevimab for the prevention of respiratory syncytial virus disease in children. Statement of the Spanish Society of Paediatric Infectious Disease (SEIP).

INTRODUCTION: Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain. OBJECTIVES: To provide recommendations for the administration of nirsevimab for prevention of RSV disease. METHODS: The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods. An expert group was formed. The group engaged in three rounds to define the questions, express support or opposition, grade recommendations and establish the agreement or disagreement with the conclusions. RESULTS: In the general neonatal population, routine administration of nirsevimab is recommended to reduce the frequency of illness and hospitalisation for bronchiolitis and RSV lower respiratory tract infection. Nirsevimab is recommended for all infants born in high-incidence RSV season and infants aged less than 6 months at the season onset. In infants born preterm between 29 and 35 weeks of gestation, with haemodynamically significant heart disease or with chronic lung disease, routine administration of nirsevimab is recommended to reduce the incidence of disease and hospitalisation due to bronchiolitis and RSV lower respiratory tract infection. In patients in whom palivizumab is currently indicated, its substitution by nirsevimab is recommended to reduce the burden of bronchiolitis. CONCLUSIONS: Routine administration of nirsevimab to all infants aged less than 6 months born during the RSV season or aged less than 6 months at the start of the winter season is recommended to reduce the burden of disease and the frequency of hospitalization due to bronchiolitis.

Zika virus screening during pregnancy: Results and lessons learned from a screening program and a post-delivery follow-up analysis (2016-2022).

OBJECTIVE: To evaluate a Zika virus screening program applied to asymptomatic exposed pregnant women. METHODOLOGY: Analysis of data generated during the roll out of a Zika screening program. We included socio-demographic data, ultrasounds, and serological results (IgM, IgG, and Plaque Reduction Neutralization Test; PRNT) from asymptomatic pregnant women exposed to Zika virus enrolled in the screening program between 2016 to 2019. RESULTS: We included 406 asymptomatic ZIKV-exposed pregnant women who gave 400 full-term new-borns. The median age was 30 years (IQR = 25-34), which was lower (29 years; IQR = 24-34) among women of non-EU migrant origin (76.4% of the sample). Migrant women tended to delay the first pre-natal consultation compared to EU origin women (p = .003). Overall, 83.2% (N = 328) of participants had ZIKV low risk serological profile (IgM-/IgG- or IgM-/IgG+ and PRNT-), 3.0% (N = 12) showed high risk of recent ZIKV infection (IgM+ or PRNT+) and 13.7% (N = 54) had indeterminate results. A fetal malformation was identified in 29 children (9.3%). Fetal malformation was associated with a ZIKV high risk serological profile [24 out of the 246 (1.6%) with low risk profile and 3 out of the 12 with at high risk profile (25.0%; p = .02)]. Four newborns with high risk profile had a positive ZIKV-PCR test, which included two cases with microcephaly. No association was observed between maternal exposure to ZIKV infection and developmental abnormalities during the post-natal period follow-up. CONCLUSIONS: The ZIKV-screening program had considerable costs and yielded a high rate of indeterminate results among asymptomatic pregnant women. Considering the poor value for decision-making of the results, efforts should focus on providing early access to routine maternity care, especially to migrant women. A simpler screening protocol might consider an initial ZIKV-PCR or IgM determination and subsequent referral to a fetal medicine specialist in those women with a positive result and/or whom ultrasound examination has revealed fetal abnormalities (10% of total women in our study sample).

The burden of non-SARS-CoV2 viral lower respiratory tract infections in hospitalized children in Barcelona (Spain): A long-term, clinical, epidemiologic and economic study.

BACKGROUND: Viral lower respiratory tract infections (LRTI) are the leading cause of hospitalization in children. In Catalonia (Spain), information is scarce about the burden of viral LRTIs in paediatric hospitalizations. The aim of this study is to describe epidemiological, clinical, virological and economic features of paediatric hospitalizations due to viral LRTI. METHODS: From October 2012 to December 2020, children aged <16 years admitted to a tertiary paediatric hospital in Catalonia (Spain) with confirmed viral LRTI were included in the study. Virus seasonality, prevalence, age and sex distribution, clinical characteristics, hospital costs and bed occupancy rates were determined. RESULTS: A total of 3,325 children were included (57.17% male, 9.44% with comorbidities) accounting for 4056 hospitalizations (32.47% ≤ 12 months): 53.87% with wheezing/asthma, 37.85% with bronchiolitis and 8.28% with pneumonia. The most common virus was respiratory syncytial virus (RSV) (52.59%). Influenza A was associated with pneumonia (odds ratio [OR] 7.75) and caused longer hospitalizations (7 ± 31.58 days), while RSV was associated with bronchiolitis (OR 6.62) and was the most frequent reason for admission to the paediatric intensive care unit (PICU) (11.23%) and for respiratory support (78.76%). Male sex, age ≤12 months, chronic conditions and bronchiolitis significantly increased the odds of PICU admission. From October to May, viral LRTIs accounted for 12.36% of overall hospital bed days. The total hospitalization cost during the study period was €16,603,415. CONCLUSIONS: Viral LRTIs are an important cause of morbidity, hospitalization and PICU admission in children. The clinical burden is associated with significant bed occupancy and health-care costs, especially during seasonal periods.

Increased RSV-A Bronchiolitis Severity in RSV-Infected Children Admitted to a Reference Center in Catalonia (Spain) Between 2014 and 2018.

Between 2014 and 2018, we evaluated the severity of 687 cases of bronchiolitis caused by respiratory syncytial virus (RSV) in Catalonia, Spain. Compared to RSV-B, RSV-A cases required intensive care (adjusted relative risk (aRR) = 1.44, p < 0.01) and respiratory support (aRR = 1.07, p < 0.01) more often; hospital stay was one day longer (p < 0.01). Subgroup identification may aid clinical evaluation and seasonal healthcare planning.

Prediction of moderate and high grade vesicoureteral reflux after a first febrile urinary tract infection in children: construction and internal validation of a clinical decision rule.

PURPOSE: Urinary tract infection leads to a diagnosis of moderate or high grade (III or higher) vesicoureteral reflux in approximately 15% of children. Predicting reflux grade III or higher would make it possible to restrict cystography to high risk cases. We aimed to derive a clinical decision rule to predict vesicoureteral reflux grade III or higher in children with a first febrile urinary tract infection. MATERIALS AND METHODS: We conducted a secondary analysis of prospective series including all children with a first febrile urinary tract infection from the 8 European participating university hospitals. RESULTS: A total of 494 patients (197 boys, reflux grade III or higher in 11%) were included. Procalcitonin and ureteral dilatation on ultrasound were significantly associated with reflux grade III or higher and then combined into a prediction model with an ROC AUC of 0.75 (95% CI 0.69-0.81). Given the prespecified constraint of achieving at least 85% sensitivity, our model led to the clinical decision rule, for children with a first febrile urinary tract infection cystography should be performed in cases with ureteral dilatation and serum procalcitonin level 0.17 ng/ml or higher, or without ureteral dilatation (ie ureter not visible) when serum procalcitonin level is 0.63 ng/ml or higher. The rule had 86% sensitivity (95% CI 74-93) with 47% specificity (95% CI 42-51). Internal cross-validation produced 86% sensitivity (95% CI 79-93) and 43% specificity (95% CI 39-47). CONCLUSIONS: A clinical decision rule was derived to enable a selective approach to cystography in children with urinary tract infection. The rule predicts high grade vesicoureteral reflux with approximately 85% sensitivity and avoids half of the cystograms that do not find reflux grade III or higher. Further validation is needed before its widespread use.