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Introduction: There are only a limited number of studies on the impact of influenza in the Spanish child population. The present work intends to increase this knowledge by studying some key aspects, such as the incidence of hospital admissions, clinic variables, comorbidities, and the vaccination status in the hospitalised children., Methods: A retrospective, observational study was conducted by reviewing the medical records of children under 15 years and hospitalised due to community acquired influenza confirmed microbiologically, during 2́flu seasons (2014-2015 and 2015-2016). The study was carried out in 10 hospitals of 6cities, which represent approximately 12% of the Spanish child population., Results: A total of 907 children were admitted to hospital with main diagnosis of influenza infection (447 <2 years), estimating an average annual rate of hospitalisation incidence of 0.51 cases / 1,000 children (95% CI; 0.48-0.55). Just under half (45%) of the cases had an underlying disease considered a risk factor for severe influenza, and most (74%) had not been vaccinated. The percentage of children with underlying diseases increased with age, from 26% in children <6 months to 74% in children >10 years. Admission to the PICU was required in 10% (92) of the cases, mainly due to acute respiratory failure., Conclusion: Influenza continues to be an important cause of hospitalisation in the Spanish child population. Children <6 months of age and children with underlying diseases make up the majority (> 50%) of the cases. Many of the severe forms of childhood influenza that occur today could be avoided if current vaccination guidelines were met., (Copyright © 2018 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Data about the management of CMV infection in pregnant women are scarce, and treatment options are very limited. The aim of the study is to investigate the effectiveness of cytomegalovirus hyperimmune globulin (CMV-HIG) for the prevention and treatment of congenital CMV (cCMV) infection., Materials and Methods: A retrospective observational study was conducted in three tertiary hospitals in Madrid. In the period 2009-2015, CMV-HIG (Cytotect ® CP Biotest, Biotest) treatment was offered to all pregnant women with primary CMV infection and/or detection of CMV-DNA in amniotic fluid in participating centers. Women were divided into prevention and treatment groups (PG and TG, respectively). Those with primary CMV infection who had not undergone amniocentesis comprised the PG and received monthly CMV-HIG (100 UI/kg). If CMV-DNA was subsequently detected in amniotic fluid, one extra dose of CMV-HIG (200 UI/kg) was given 4 weeks after the last dose. Those women were considered to be part of the PG group despite detection of CMV-DNA in amniotic fluid. In the case of a negative result in CMV-DNA detection in amniotic fluid or if amniocentesis was not performed, monthly HIG was given up to the end of the pregnancy., Results: Thirty-six pregnant women were included. Median gestational age at birth was 39 weeks (interquartile range: 38-40) and two children (5.5%) were premature (born at 28 and 34 weeks' gestation). Amniocentesis was performed in 30/36 (83.4%) pregnancies and CMV PCR was positive in 21 of them (70%). One fetus with a positive PCR in amniotic fluid that received one dose of HIG after amniocentesis presented a negative CMV-PCR in urine at birth, and was asymptomatic at 12 months of age. Twenty-four children were infected at birth, and 16/21 (76.2%) presented no sequelae at 12 months, while two (9.5%) had a mild unilateral hearing loss and three (14.3%) severe hearing loss or neurological sequelae. Seventeen women were included in the PG and 19 in the TG. In the PG 7/17 (41%) fetuses were infected, one pregnancy was terminated due to abnormalities in cordocentesis and one showed a mild hearing loss at 12 months of age. In the TG, 18/19 children (95%) were diagnosed with cCMV, while the remaining neonate had negative urine CMV at birth. Eight out of the 19 fetuses (42.1%) showed CMV related abnormalities in the fetal US before HIG treatment. Complete clinical assessment in the neonatal period and at 12 months of age was available in 16 and 15 children, respectively. At birth 50% were symptomatic and at 12 months of age, 4/15 (26.7%) showed a hearing loss and 3/15 (20%) neurologic impairment. Fetuses with abnormalities in ultrasonography before HIG presented a high risk of sequelae (odds ratios: 60; 95%CI: 3-1185; p = .007)., Discussion: Prophylactic HIG administration in pregnant women after CMV primary infection seems not to reduce significantly the rate of congenital infection, but is safe and it could have a favorable effect on the symptoms and sequelae of infected fetuses. The risk of long-term sequelae in fetuses without US abnormalities before HIG is low, so it could be an option in infected fetuses with normal imaging. On the other hand, the risk of sequelae among infected fetuses with abnormalities in fetal ultrasonography before HIG despite treatment is high.

Objective: Kingella kingae is a common colonizer of the oropharynx in children that may lead to invasive infection, mainly osteoarticular infections. Invasive infections occur almost exclusively in young children, fundamentally fewer than two years old. K. kingae infections in children are probably underdiagnosed due to the difficulty in growing in routine cultures and the absence of systematic realization of molecular techniques to identify it. It is the most common bacteria involved in childhood osteoarticular infections in recent series and increasingly being recognized in Spain. We report our experience on the epidemiological and clinical characteristics of osteoarticular infections in children in recent years., Methods: Retrospective analysis of septic arthritis by K. kingae identified by PCR in joint fluid in children during 2010-2016. Epidemiological, clinical and laboratory characteristics are presented., Results: Five arthritis by K. kingae were identified, all of them in ≤6 years old children. Median leukocytes, CRP and ESR were 12950 leukocytes/μL, 4.84 mg/dL and 58 mm/h respectively, and 61,322 leukocytes /μL in joint fluid. All patients evolved favorably., Conclusions: Osteoarticular infections by K. kingae in children usually present low increase of inflammatory markers despite being invasive infections. The development of PCR in sterile samples has greatly improved the diagnostic yield of K. kingae infections improving the management of osteoarthritis in children., (©The Author 2018. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background: Weekends off antiretroviral therapy (ART) may help engage HIV-1-infected young people facing lifelong treatment. BREATHER showed short cycle therapy (SCT; 5 days on, 2 days off ART) was non-inferior to continuous therapy (CT) over 48 weeks. Planned follow-up was extended to 144 weeks, maintaining original randomisation., Methods: BREATHER was an open-label, non-inferiority trial. Participants aged 8-24yrs with virological suppression on efavirenz-based first-line ART were randomised 1:1, stratified by age and African/non-African sites, to remain on CT or change to SCT. The Kaplan-Meier method was used to estimate the proportion of participants with viral rebound (confirmed VL≥50 copies/mL) under intent-to-treat at 48 weeks (primary outcome), and in extended follow-up at 96, 144, and 192 weeks. SCT participants returned to CT following viral rebound, 3 VL blips or discontinuation of efavirenz., Findings: Of 199 participants (99 SCT, 100 CT), 97 per arm consented to extended follow-up. Median follow-up was 185.3 weeks (IQR 160.9-216.1). 69 (70%) SCT participants remained on SCT at last follow-up. 105 (53%) were male, baseline median age 14 years (IQR 12-18), median CD4 count 735 cells/μL (IQR 576-968). 16 SCT and 16 CT participants had confirmed VL≥50 copies/mL by the end of extended follow-up (HR 1.00, 95% CI 0.50-2.00). Estimated difference in percentage with viral rebound (SCT minus CT) by week 144 was 1.9% (90% CI -6.6-10.4; p = 0.72) and was similar in a per-protocol analysis. There were no significant differences between arms in proportions of participants with grade 3/4 adverse events (18 SCT vs 16 CT participants; p = 0.71) or ART-related adverse events (10 vs 12; p = 0.82). 20 versus 8 serious adverse events (SAEs) were reported in 16 SCT versus 4 CT participants, respectively (p = 0.005 comparing proportions between groups; incidence rate ratio 2.49, 95%CI 0.71-8.66, p = 0.15). 75% of SAEs (15 SCT, 6 CT) were hospitalisations for a wide range of conditions. 3 SCT and 6 CT participants switched to second-line ART following viral failure (p = 0.50)., Conclusions: Sustainable non-inferiority of virological suppression in young people was shown for SCT versus CT over median 3.6 years. Standard-dose efavirenz-based SCT is a viable option for virologically suppressed HIV-1 infected young people on first-line ART with 3-monthly VL monitoring., Trial Registration: EudraCT 2009-012947-40 ISRCTN 97755073 ClinicalTrials.gov NCT01641016.

Background: Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is endemic in Latin-America and is emerging in Spain due to immigration. The vertical transmission rate is around 5%. A routine prenatal screening with serology of all pregnant women from endemic areas is recommended to identify infected newborns, allowing early treatment and cure., Objective: The aim of this study was to estimate the prevalence of positive Chagas serology in a cohort of pregnant women from Latin-America and its vertical transmission., Patients and Methods: An observational, prospective, follow-up study was conducted on women with positive serology to T. cruzi, as well as their newborns, from January 2013 to April 2015. Congenital Chagas was ruled out using a PCR technique at birth and at 1 month, and with serology at 9-12 months old. A child was considered infected when PCR was positive, and uninfected when PCR was negative, and/or it had a negative serology., Results: Screening was performed on 1244 pregnant women from Latin-America, and there were positive results in 40 (prevalence 3.2%, 95% CI: 2.4-4.4%), with 85% of them from Bolivia. There was only one infected newborn (rate of vertical transmission 2.8% (95% CI: 0-15%)), who had a positive PCR at birth. Relative studies enabled an 8-year-old sister with an asymptomatic disease to be diagnosed and treated. Both were treated successfully with benznidazole (later the PCR and serology were negative)., Conclusion: Screening during pregnancy in Latin-American women helped to detect those with Chagas disease. The rate of vertical transmission was 2.8%, in keeping with literature. Screening led to the detection and treatment of previously unidentified familial cases., (Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Tuberculosis (TB) is the most important infectious disease all over the world, with a high morbidity and mortality. Pediatric tuberculosis has been a neglected epidemic, due to the difficulties in assessing its global impact, reduced incidence and lower infectivity compared to adults. In 2015, the WHO reported 1 million cases of paediatric TB and 169,000 deaths. In Europe, the emergence of MDR TB is a major concern, representing 16% of the new diagnosis in Eastern Europe. In 2014, it was estimated that about 219,000 children were infected by MDR-TB-strains in Europe, and 2,120 developed the disease. Spain is the Western European country with more paediatric cases, with an incidence 4.3/100,000 inhabitants in 2014. Paediatric tuberculosis mortality in Spain is rare, but extra-pulmonary disease is associated with significant complications. The prevalence of paediatric drug resistant TB in Spain is over 4%, higher than the estimated incidence in adult population, representing mayor difficulties for therapeutic intervention. These data reveal that paediatric TB is still a Public Health priority in our country. The difficulties in diagnosis and the lack of optimal paediatric drug formulations are the major challenges for controlling the childhood's tuberculosis epidemic. A group of national paeditric TB experts has reviewed the international guidelines and the most recent evidences, and has established new recommendations for the management of paediatric TB contacts, latent infection and active TB disease, especially focused in drug resistant cases. This document replaces the former national guidelines from the Spanish Society for Pediatric Infectios Diseases, although the prior recommendations on the diagnosis remain valid., (Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Polymerase chain reaction (PCR) assays have shown to be useful and quick for the diagnosis of enterovirus in aseptic meningitis. The aim of our study was to analyse the changes in clinical practice after the introduction of a real-time polymerase chain reaction (RT-PCR) technique using the Xpert EV (Cepheid ® ) assay for the qualitative detection of enterovirus RNA in cerebrospinal fluid specimens from children with suspected viral meningitis., Methods: A retrospective study was performed in children older than 1year, diagnosed with enterovirus meningitis in a third level hospital from November 2006 to February 2013. The first period, before the availability of Xpert EV (Cepheid ® ) (Group1, November 2006-August 2010) was compared with the later period (Group2, September 2010-February 2013). Clinical characteristics, the mean length of stay, and the cost per inpatient cases, were compared between the 2periods., Results: Forty-one patients (60.9% male) were included, with a median age of 64 months (interquartile range 28-96). Twenty-six patients (63.4%) were included in Group2. There were non-statistically significant differences in the epidemiological, disease severity, and laboratory characteristics between both periods of study. A significant difference was observed in the mean length of stay, with it being shorter in Group2 (48hours vs 40.5hours, P=.039), and a significant lower inpatient cost per case (€779.77 vs €656.05, P<.05)., Conclusion: Xpert EV (Cepheid ® ) assay was useful for decreasing the length of hospital stay and the costs associated with hospitalisation in children with enterovirus meningitis., (Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Influenza virus infection is a major health care burden and is associated with significant morbidity and mortality. The 2009 influenza pandemic highlighted the importance of influenza surveillance. The objective of this study was to assess the epidemiology and activity of influenza A and B viruses in adults and children in the post-pandemic period with a special focus on the pediatric population. We performed a retrospective descriptive study involving adults and children with influenza-like illness at the Clinico San Carlos Hospital (Madrid, Spain) over six influenza seasons, between August 2010 and April 2016. Respiratory specimens were collected from 3131 patients and routinely processed for influenza diagnosis. Epidemiological analysis was performed in terms of gender, age, and seasonal distribution. Globally, Influenza A and B viruses were detected in the respiratory specimens of 696 (22.2%) of the 3131 studied population. Among all influenza positive specimens, 142 (20.4%) were influenza A(H1N1)pdm09, 61 (8.8%) were influenza A(H3N2), 321 (46.1%) were untypeable influenza A viruses and 166 (23.9%) were influenza B. Co-infection by both influenza A and B viruses was detected in six patients (0.9%). Meanwhile, co-infection with other non-influenza respiratory viruses was identified in 5 children and 20 adults. Influenza A(H1N1)pdm09 virus activity has been significantly high since the 2009 pandemic and has gradually replaced the previously circulating seasonal influenza A(H1N1) virus. Moreover, influenza A(H3N2) virus activity remained at low levels during the last winter season while influenza B virus isolates increased significantly over the past 2 years., (© 2017 Wiley Periodicals, Inc.)

Reported synonymous substitutions are generally non-pathogenic, and rare pathogenic synonymous variants may be disregarded unless there is a high index of suspicion. In a case of IL7 receptor deficiency severe combined immunodeficiency (SCID), the relevance of a non-reported synonymous variant was only suspected through the use of additional in silico computational tools, which focused on the impact of mutations on gene splicing. The pathogenic nature of the variant was confirmed using experimental validation of the effect on mRNA splicing and IL7 pathway function. This case reinforces the need to use additional experimental methods to establish the functional impact of specific mutations, in particular for cases such as SCID where prompt diagnosis can greatly impact on diagnosis, treatment, and survival.

Unlabelled: Advances in care and antiretroviral treatment, improved life expectancy and quality of life in children with perinatally-acquired human immunodeficiency virus (HIV) infection. There is increasing interest in the chronic effects of growing up with HIV. The aim of this study was to assess the psychosocial, emotional and behavioural functioning in a cohort of perinatally-acquired HIV-infected adolescents. Data were obtained through semi-structured interviews and the Strengths and Difficulties Questionnaire (SDQ) for emotional and behavioural disorders screening., Results: A total of 95 patients (58% women) were assessed with a median age of 15 years (11-19.1) and a median age at diagnosis of 1.7 years (0-12.2). The median CD4 count, at the inclusion, was 626 cells/mm(3) (132-998), with 34% (10-52%). Viral load was <50 copies/ml in 72% of patients. Eighty-one per cent knew their diagnosis and optimal adherence was achieved in 53%. Passive coping was reported in 58.4% of the adolescents. Only 7.7% of teenagers had a complete and adequate knowledge of their disease and only 18.2% had shared it with their friends. Six unwanted pregnancies occurred (11% of women). Most of them (90%) attended school but 60% had been held back one or more school years. Overall, SDQ scored a risk of behavioural and emotional problems in 24.5%. The report of behaviours associated with hyperactivity was high in 14.9% of the population and borderline in 18.1%. Adolescents with encephalopathy accounted for 44% of those whose total scores fell in either the abnormal and borderline ranges for emotional difficulties (p = .038)., Conclusion: Perinatally-acquired HIV-infected adolescents showed significant psychosocial and behavioural health risks that should bring attention to prevention and health care programmes. An earlier disclosure to children could favour a better psychological adjustment and a better treatment adherence. Future studies are needed to assess the relationship between vertically acquired HIV-infection and hyperactivity.

Background: Successful antiretroviral therapy (ART) has dramatically reduced mortality among HIV-infected children. However, there is growing concern about long-term effects associated to ART. The aim of this study was to determine the prevalence of metabolic abnormalities in a cohort of perinatally HIV-infected adolescents and young adults and to identify associated factors., Methods: We present results from a cross-sectional analysis including individuals 12 to 20 years of age, from a prospective, longitudinal cohort of perinatally-acquired HIV-infected children, adolescents and young adults in Madrid. Clinical and immunological data were recorded and complete lipid and glycemic profiles were determined., Results: Ninety-nine adolescents were included, with a median age of 15.3 years [13.6-16.7]. Patients with abnormal levels of lipids were as follows: 27.2% total cholesterol ≥200 mg/dl, 25.9% LDL cholesterol (LDL-c) ≥ 130 mg/dl, 14.1% HDL-C < 35 mg/dl and 39.8% triglycerides ≥ 150 mg/dl. Current use of protease inhibitors (PI) was associated with higher triglyceride values (p = 0.022). Four (4.6%) patients showed fasting glucose ≥ 100 mg/dl and 30.6% presented with insulin resistance (IR) (HOMA-IR over the 90th centile). In the multivariate logistic regression analysis adjusted for sex, age, weight, Tanner stage, protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors (NRTI) treatment length and CD4 nadir, IR was associated with higher waist circumference Z score; OR: 3.92(CI95%: 1.15-13.4) (p = 0.03)., Conclusion: There was a high prevalence of insulin resistance and lipid abnormalities in this cohort of perinatally-acquired HIV-infected adolescents. A simple clinical measurement like waist circumference Z score might be a reliable marker and predictor of insulin resistance in these patients.

Introduction: Thanks to advances in antiretroviral treatment, children with HIV infections through vertical transmission have improved their life expectancy. However, new challenges have emerged. We propose this study in order to determine the psychosocial aspects and knowledge of infections in a cohort of adolescents with vertically transmitted HIV infections., Methods: Patients with vertically-acquired HIV infection between 12 and 19 years old were included. Data were obtained through semi-structured interviews and a Strengths and Difficulties Questionnaire for emotional and behavioral disorders screening., Results: We evaluated 96 patients (58% females) with a median age of 15 years (11-19.1) and a median age at diagnosis of 1.70 years (0-12.2). The median CD4 count was 626cells/mm(3) (132-998), and the viral load was<50cp/ml in 72% of patients. Among them, 90% attended school and 60% repeated at least one course. Although 81% of them knew of their diagnosis, only 30% understood their disease, with 18.2% having discussed it with friends. Six unwanted pregnancies occurred during the study period. Strengths and Difficulties Questionnaire showed hyperactivity risk in 33%., Conclusion: A high percentage of adolescents show difficulties in several areas (disease knowledge, peer relationship, school failure...) that can have an impact on their adult lives. Further studies are needed to evaluate their origin and development in depth, as well as interventions to modify this situation., (Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

We evaluated the evolution over time of once-daily antiretroviral therapy in HIV-infected children and its relationship with adherence. An increase on the prevalence of once-daily antiretroviral therapy was observed over time (from 0.9% in 2002 to 44.2% in 2011). There was no difference in adherence regarding once-daily or BID regimens in 2011. Adherence was related to age and pill burden.

Purpose: Fosamprenavir, combined with low-dose ritonavir (FPV/r), is indicated for treatment of HIV-infected children aged ≥ 6 years in Europe. Our purpose was to assess the safety of licensed use of FPV/r in HIV-infected children reported to six cohorts in the European Pregnancy and Paediatric HIV Cohort Collaboration., Methods: Retrospective analysis of individual patient data for all children aged 6-18 years taking the licensed dose of FPV up to 31/12/10. Adverse events (clinical events and absolute neutrophil counts, total cholesterol and triglycerides, and alanine transaminase) were summarised and DAIDS gradings characterised severity., Results: Ninety-two HIV-infected children aged 6-18 years took the licensed dose, comprising 3% of the total number of children in follow-up in participating cohorts. Median age at antiretroviral therapy initiation was 6 years (interquartile range 1-11 years), and median age at start of FPV/r was 15 years (12-17 years). Estimated median time on an FPV-containing regimen was 52 months, with a total of 266.9 patient years of exposure overall. Half (54%) were on an FPV-containing regimen at last follow-up. Rates of grade 3/4 events were generally low for all biochemical toxicity markers, and no serious adverse events considered to be causally related to FPV/r were reported., Conclusions: Results suggest that long-term licensed dose FPV-containing regimens appear to be generally well tolerated with few reported toxicities in HIV-infected children in Europe, although relatively infrequently prescribed. No serious events were reported

Background: Mycobacterium lentiflavum is considered a rare pathogen causing nontuberculous mycobacterial (NTM) lymphadenitis., Methods: A multicenter, retrospective study was performed in immunocompetent children <14 years of age with microbiologically confirmed NTM lymphadenitis treated at 6 hospitals in Madrid, Spain, during 2000-2010. We compared children with M. lentiflavum and Mycobacterium avium-intracellulare complex infection., Results: Forty-five microbiologically confirmed NTM lymphadenitis patients were identified: 19 (45.2%) caused by M. avium-intracellulare complex, 17 (40.5%) by M. lentiflavum, 1 by both and 5 by other mycobacteria. Out of 17 M. lentiflavum cases, 14 were diagnosed in the past 5 years. Regarding M. lentiflavum cases, median age was 23 months. Submandibular nodes were the most frequently involved (76.5%), with multiple locations seen in 41% of the children and spontaneous drainage in 41% of them. Drug susceptibility tests were performed in 14 isolates and showed a complete susceptibility to clarithromycin and cycloserine, whereas 93% were resistant to rifampin, 33% to quinolones and full resistance to other tested antimycobacterial drugs was detected. All but 1 child required surgery and 11 were treated additionally with various drug combinations. Total resolution was achieved in 50% of children within 6 months.Compared with M. avium-intracellulare complex cases, children were younger and laterocervical nodes were significantly less frequently involved. No statistically significant differences were found related to clinical characteristics, treatment and outcome., Conclusions: M. lentiflavum is an emerging pathogen producing NTM lymphadenitis in Madrid.

Congenital toxoplasmosis is the result of transplacental fetal infection by Toxoplasma gondii after the primary maternal infection. The severity of the disease depends on the gestational age at transmission. First trimester infections are more severe, but less frequent, than third trimester infections. Acute maternal infection is diagnosed by seroconversion or by the detection of IgM antibodies and a low IgG avidity test. In these cases, spiramycin should be initiated to prevent transmission to the fetus. For identification of fetal infection, polymerase chain reaction (PCR) testing of amniotic fluid after 18 weeks gestation should be performed. If fetal infection is confirmed, the mothers should be treated with pyrimethamine, sulfadiazine and folinic acid. Most infants infected in utero are born with no obvious signs of toxoplasmosis, but up to 80% developed learning and visual disabilities later in life. Neonatal diagnosis with IgM/IgA antibodies or blood/cerebrospinal fluid PCR may be difficult because false-negative results frequently occur. In these cases diagnosis is possible by demonstrating a rise in IgG titers during follow-up or by the detection of antibodies beyond one year of age. Early treatment with pyrimethamine and sulfadiazine may improve the ophthalmologic and neurological outcome. Congenital toxoplasmosis is a preventable disease. Pre-pregnancy screening and appropriate counseling regarding prevention measures in seronegative women may prevent fetal infection., (Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Background and Aims: The present study focuses on the epidemiology, clinical and laboratory data, and management of osteomyelitis in a pediatric third level hospital., Methodology: All cases of children under 15 years-old admitted with osteomyelitis between 2000 and 2011 were retrospectively reviewed until July 2006, then prospectively from then until 2011., Results: A total of 50 patients were identified (52% males) with median age at diagnosis of 2 years. Principal onset manifestations were pain (94%), functional impairment (90%) and fever (72%). The femur (32%), fibula (28%) and calcaneus (22%) were most affected bones. Leucocytosis > 12.000/μl was found in 56%, elevated ESR > 20 mm/h in 26%, and elevated CRP > 20 mg/L in 64%. Blood culture was positive in 20%, with group A streptococcus being the most frequently isolated bacteria (11%). All diagnoses were confirmed by a (99)Tc scintigraphy bone scan. Antibiotic therapy was initially intravenously (mean time of administration: 10 days ± 3 SD), followed by oral medication (mean time of administration: 18 days ± 6 SD). Surgery was necessary in 3 patients. Evolution of all cases was excellent, despite 3 exceptions that resolved over time., Conclusions: The current short-term intravenous therapy led to shorter hospitalizations. There were no statistically significant differences between time from clinical onset or in CRP levels at discharge compared to long-term therapies prior to 2006., (Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier España, S.L. All rights reserved.)

Background: Diagnosis of pulmonary tuberculosis (PTB) is difficult in infants and young children. For microbiological confirmation of PTB children, sequential gastric lavage (GL) is recommended. Induced sputum (IS) may be an alternative or complementary tool, but the information is limited in children in developed countries. The aim of this study is to assess the safety and diagnostic yield from IS combined with GL for PTB diagnosis in non-HIV infected children., Methods: The study involved 22 children with suspected PTB admitted to the Getafe Hospital from January 2007 to May 2011. IS and GL were performed on three consecutive days, according to a standardized protocol. In all samples, BK staining, culture and PCR were carried out, including Genotype MTBDR plus for resistance to INH-RIF (Isoniazid-Rifampin) since 2008. A preliminary analysis of an ongoing prospective study is presented., Results: Median age was 72 months (range 1 month to 14 years of age). Seven (33%) were ≤ 5 years of age. Seventeen were clinically diagnosed of PTB based on positive PPD and radiological criteria. Microbiological confirmation was achieved in 10 (58.8%) by either GL or IS. M. tuberculosis was identified by GL in 8 children (47.1%) and by IS in 7 (41.2%). One infant (2 IS samples) had transient oxygen desaturation recovered spontaneously., Conclusions: IS appears to be safe and well tolerated by children for diagnosis of PTB and is more convenient. Increasing the diagnostic yield of PTB in children with PTB may be a complementary technique. Largest studies are necessary to define the role of IS in paediatric PTB.

Background: Mother-to-child transmission (MTCT) during pregnancy, delivery or breastfeeding, is the main route of HIV infection in children. Strategies aimed at promoting the health of HIV infected pregnant women and MTCT prevention have reduced transmission to below 2%. This paper presents the clinical and epidemiological features of a cohort from Madrid and compares foreign-born with Spanish-born women., Method: Retrospective, observational and descriptive study on HIV infected pregnant women from South Madrid (n=70) and their offspring (n=78) who were born during the study period from August 1992 to January 2010., Results: Most pregnant women were infected by heterosexual transmission (51%). Most Spanish-born women (66%) were diagnosed before pregnancy (81%), while foreign-born women (34%) were diagnosed during pregnancy (70%). Foreign-born women had less obstetric check-ups (67%) than Spanish-born women (97%). The MTCT rate was 1.3% during the last ten years., Conclusions: Heterosexual transmission is the primary mode of acquisition of HIV infection both for Spanish-born and foreign-born pregnant women. However, the HIV infection was diagnosed earlier in Spanish-born women. There were no differences in the effectiveness of antiretroviral therapy as a preventive measure against MTCT when it is started at an early stage., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Introduction: Since 1996, when HAART became available, there has been a change in the course of HIV-infection, leading it to become a chronic disease. Our aim was to describe the characteristics of the children followed up in our hospital., Patients and Methods: A cross-sectional study was conducted on 32 HIV-infected children followed up until December-2010, at the University-Hospital de Getafe. Clinical and laboratory information from the last visit was collected for the evaluation of patients., Results: Thirty-two children with HIV-1 were evaluated, 29 infected through vertical-transmission. The median age was 14 years. According to the CDC classification, 56% (18/32) of children were in category A, 28% (9/32) B and 16% (5/32) C. Immunological class was 3 in 75% of children, class 2 in 9% and class 1 in 16%. The median nadir of CD4 was 337 cells/ml (12%). The median current CD4 was 749 (31%). Only one adolescent had a CD4% below 200 cells/ml due to lack of adherence. Twenty-eight patients (87%) were receiving HAART, and 4 patients were off antiretroviral treatment. Among the patients treated, 26 (93%) had viral loads <200 copies/ml. The median viral-load was<20 copies/ml. Median time on antiretroviral treatment was 10 years. The combination more frequently used was two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI), that was given to 15 patients (47%), followed by 2 NRTI, and one non-nucleoside reverse transcriptase inhibitor (NNRTI) in 8 patients (29%). Two children received rescue therapy including raltegravir, one with tipranavir and the other with darunavir. A total of 12 patients (43%) received medication once a day, 7 of them with fixed-dose combinations in a single tablet (25%). There were metabolic complications, including hyperlipidaemia or lipodystrophy were observed in 17 children (53%)., Conclusions: Most of our patients are receiving HAART, with good virological and immunological control. The prevalence of metabolic abnormalities was high. Strategies to improve adherence and decrease toxicities are needed in perinatally-acquired HIV-infected children., (Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Background and Objectives: «PFAPA syndrome» is an autoinflammatory entity consisting of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis. Its etiology is unknown although a dysregulation in the control of the autoinflammatory response seems to play a role. Although a genetic origin is suspected, no specific mutation has been determined yet. Corticosteroids are the mainstay of the treatment during the acute attacks. However, in long-term follow-up the role of tonsillectomy is controversial., Patients and Methods: A retrospective study of the pediatric cases diagnosed with the PFAPA syndrome was performed in our center during the last 4 years., Results: Ten patients were diagnosed with the syndrome who received corticosteroids as the only treatment with improvement and favourable prognosis., Conclusion: PFAPA syndrome is the most common periodic fever disorder described in childhood whose genetic background has not been yet clarified. Our contribution with 10 patients further supports the common existence of this entity and the need to keep it in mind when having recurrent fevers., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Unlabelled: "PFAPA syndrome" is an autoinflammatory entity composed of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. There have been many reports of children with the disease, but only occasionally have been described in siblings, and no specific genetic mutation has been determined yet. Corticosteroids are the mainstay in the treatment of the acute attacks. The role of surgery in long-term follow-up (tonsillectomy with or without adenoidectomy) is controversial. We report two brothers affected with the syndrome, in whom corticosteroids as the only treatment led to an improvement. A genetic work-up was performed, making very unlikely other possible syndromes of recurrent fever., Conclusion: PFAPA syndrome is the most common recurrent periodic fever disorder described in childhood. Its genetic background has not been elucidated yet. Our contribution with two siblings affected with PFAPA syndrome further support the genetic basis for the entity.

Micafungin is an echinocandin approved by the European Medicines Evaluation Agency for the treatment of invasive candidiasis in children, including premature infants born before 29 weeks of pregnancy, and as prophylaxis in children undergoing hematopoietic stem-cell transplantation or patients at risk of prolonged neutropenia. This drug has good activity in several Candida spp., including those resistant to fluconazole. Although micafungin is active against Aspergillus spp., it has been used mainly in combination therapy for invasive aspergillosis. There is ample information on the use of micafungin in children, including neonates, and this drug is the only echinocandin approved for use in infants aged less than 3 months. The efficacy, pharmacokinetics and safety of micafungin have been evaluated in phase II and III clinical trials in children, in which its efficacy and safety were demonstrated in comparison with liposomal amphotericin B and fluconazole. The pharmacokinetic profile of micafungin in children allows once daily intravenous administration, with greater clearance than in adults, and consequently pediatric doses are relatively higher. The most appropriate dose in children weighing less than 40 kg is 2 mg/kg/day in the treatment of invasive candidiasis and 1 mg/kg/day as prophylaxis in children undergoing hematopoietic stem-cell transplantation. Doses in neonates should be higher. In premature infants, the most appropriate doses to achieve levels in the brain parenchyma are 7 mg/kg/day and 10 mg/kg/day in those weighing more and less than 1,000 g, respectively. Micafungin has few drug-drug interactions and an acceptable safety profile. Withdrawal of this drug due to adverse effects is rare, although transaminase monitoring is recommended during treatment, as well as evaluation of the risk-benefit balance in patients with liver disease or concomitant administration of hepatotoxic drugs., (Copyright © 2011 Elsevier España S.L. All rights reserved.)

Introduction: Kawasaki disease is the leading cause of acquired heart disease in children. In spite of the efficacy of intravenous immunoglobulin (IGIV), the absence of a specific diagnostic test and due to there being IGIV-refractory patients, Kawasaki disease is a major cause of coronary artery abnormalities (CAA)., Objectives: To analyze the clinical and epidemiological characteristics of cases of Kawasaki disease, to evaluate the efficacy of treatments used and the CAA observed., Methods: We retrospectively reviewed the medical records of children diagnosed with Kawasaki disease between January 2002 and December 2008 in a tertiary public Hospital in the South of Madrid. The diagnosis of Kawasaki disease was based on the clinical criteria proposed by the American Academy of Pediatrics in 2004., Results: Twenty three children were identified. Median age was 26 months (range: 2 months-10 years). Nineteen children (82%) were younger than 5 years old. Fever and changes in the lips and oral cavity were present in all cases. Twenty-one patients (91%) received IGIV, all of them before the 10th day of disease. One child (4.7%) required the administration of more than one dose of IGIV, because persistence of fever. CAA was recorded in three patients [13.0%, (95% CI: 1-26%)], including a four month-old boy. All patients with CAA were treated with the recommended dose of IGIV, 2g/kg, between the 5th and 8th day of disease., Conclusions: Kawasaki disease was more common in children less than five years old. We observed a high rate of CAA in children with Kawasaki disease in spite of appropriate and timely treatment., (2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Introduction: Visceral leishmaniasis is endemic in Spain. New diagnostic tools and shorter regimens of treatment are been increasingly being used in children., Objectives: To analyze the clinical and epidemiological characteristics of cases of visceral leishmaniasis, to evaluate the diagnostic techniques tested and the safety and efficacy of treatments used., Methods: We retrospectively reviewed the medical records of children diagnosed with visceral leishmaniasis between January 1994 and December 2007 in a tertiary public Hospital in the South of Madrid. The diagnosis of visceral leishmaniasis was based on visualization of Leishmania sp. in bone marrow aspirate or culture or positive PCR analysis of the bone marrow aspirate., Results: Eleven immunocompetent children were identified. Median age was 21 months (range: 4 months - 13 years). Fever was present in all cases, and hepatomegaly and splenomegaly in 10 (91%). Anemia was the most frequent haematological finding (100%). A bone marrow aspirate was obtained in all cases. Leishmania amastigotes were observed in 8 (73%) cases. Leishmania DNA in the bone marrow aspirate was detected in all patients who underwent this procedure. Positive immunofluorescent-antibody test (IFAT) analysis at baseline was observed in 63% of cases tested. The threshold titer for positivity was 1/40. Urinary antigen detection test was positive in 4 out of 6 (67%) children in whom I was performed. Initial treatment consisted of meglumine antimoniate in 3 patients and liposomal amphotericin B (LAB) in 8 (73%) patients. All children had an early clinical response. Only one child treated with LAB relapsed. No severe adverse events were observed with treatment., Conclusions: Visceral leishmaniasis is still a common disease in our area. Clinical and laboratory findings of visceral leishmaniasis are similar to other Mediterranean area reports. PCR analysis of the bone marrow aspirate was more sensitive than traditional diagnostic techniques. Non-invasive diagnostic techniques may be used as an aid in the diagnosis of visceral leishmaniasis in children. Short course treatment of visceral leishmaniasis with liposomal amphotericin B has been safe and effective., (Copyright 2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Introduction: Recent reports show that Antiretroviral Treatment (ART) during pregnancy does not affect somatic growth of children born to HIV-infected mothers, are reassuring. The aim of this study is to perform an anthropometric analysis of the uninfected children followed in the Spanish FIPSE cohort during their first 18 months of life, and to describe the possible risk factors during pregnancy that may influence low birth weight., Methods: The FIPSE cohort includes 8 public hospitals in Madrid, and prospectively follows children born to HIV-infected women at these hospitals. We collected data on 601 uninfected children, following standardised protocols, during their first 2 years of life. A P value<0.05 was considered statistically significant. Data from the Pablo Orbegozo Foundation were used to compare the means of our population with the standard weight, longitude an occipitofrontal circumference (OFC) of the Spanish population during the first 18 months of life., Results: The mean weight was 2766g (+/-590), and 2967g (+/-427) when premature neonates were excluded. The proportion of Intrauterine Growth Restriction among non- premature neonates was 19.8% (95% CI: 16.3-23.8). Children born to mothers that used illicit drugs weighed less: 2752g (+/-325) vs. 3002g (+/ 435), P<0.001, as did children born to mothers who smoked during pregnancy: 2842g (+/-363) vs. 3018g (+/-444), P>0.001. Maternal anaemia did not influence the low birth weight of the children when premature neonates were excluded. We found no statistically significant differences depending on the ART received during pregnancy. Children born to mothers who had CD4 > 500 cell /mm were heavier (2834g +/-503) than those whose mothers had CD4 of less than 200 cell/mm (2565g +/-702), P=0.008. These differences disappeared when premature neonates were excluded. Children born to mothers with undetectable viral load were heavier (2866g +/-532 vs. 2704g +/-588, P=0.005), but these differences also disappeared when the prematures were excluded from the analysis. Mean weight, length, and OFC of our population at birth (excluding premature neonates) were lower than the Spanish standards. (z for weight=-0.83; z for length =-1.02; z for OFC=-1.00), but these differences are not statistically significant and disappear at 18 months of age (z for weight=-0.08; z for height=-0.32; z for OFC=-0.31). The type of ART did not have any significant influence., Discussion: There is a very significant difference between the weight of the children born to mothers addicted to illicit drugs and the rest of the children. Similarly, the weight of the children born to smoking mothers is significantly lower. There was no association between maternal anaemia and the type of ART. The children of our population have lower weights, length and OFC at birth, but this may due to the high number of scheduled caesarean births, practised at 38 weeks of pregnancy (54.5%). Our children catch-up with anthropometric measurements during the first and second year of life, and these are similar to Spanish standards at 18 months old.

Introduction: Malaria has increased in Spain, and is potentially severe in children. Information on pediatric malaria in Spain is scarce. The aim is to evaluate the clinical, therapeutic and epidemiological characteristics of children diagnosed with malaria in our hospital., Patients and Methods: A retrospective descriptive study was performed on all pediatric cases of malaria diagnosed in Getafe University Hospital, from January 1995 to November 2006. Epidemiological and clinical features, as well as diagnostic methods, treatments and outcome were studied. An analysis of two comparative periods (before and after January 2000) was carried out., Results: Eighteen cases of confirmed malaria were identified, twelve girls and six boys. The age range was from 13 months to 13 years with a median age of 60 months. All patients had recently travelled to or from endemic countries. Despite having a stable number of admissions to hospital over time, all but two patients were diagnosed in the second period (P<0.01). Fever and gastrointestinal symptoms were the most common symptoms, with liver or spleen enlargement in 75%. Thrombocytopenia and anemia were common. No cases of complicated malaria or death occurred. Plasmodium identification by microscopic examination was used in all cases. Identification of Plasmodium species with PCR was carried out in 16 children. P. falciparum was found in 89% of these cases. Quinine-sulphate and clindamycin were used in 72%., Conclusions: The incidence of pediatric malaria is increasing in the southern area of Madrid, with P. falciparum as the most frequently identified species. Microscopic visualization or identification of its antigen are gold-standard diagnostic methods, however, identification with PCR is essential upon admission to determine the species and discard possible multiple infestations. Pediatricians must learn to suspect this potentially severe disease, in order to establish an early treatment that may improve the prognosis.

Introduction: Mother-to-Child HIV transmission is now just 1% in western countries, due to prevention measures. Antiretroviral Treatment (ART) drugs do have adverse effects, anaemia and myelosupression caused by cidovudina being the most commonly observed effects. In the present study, we have analysed the proportion and characteristics of congenital malformations (CM) or birth defects (BD) in a cohort of uninfected children born to HIV-infected women., Methods: A total of 623 uninfected children belonging to the FIPSE cohort were followed up according to standardised protocols. This cohort includes 8 public hospitals from Madrid and follows up HIV-infected pregnant women and their children. Children were classified according to prematurity, ethnic origin, birth weight, withdrawal syndrome, in-utero treatment. Birth defects were described and defined according to the EUROCAT, the European registry for BD. Mild errors of morphogenesis were excluded from the analysis. Categorical variables were compared with the X(2) or the Fisher test., Results: A total of 78% (486) of the mothers were of Caucasian origin; 18.8% (117) used some illicit drug (heroine, cocaine or methadone) during gestation; 51 mothers (8.1%) received no ART, 10 (1.6%) received monotherapy and 469 (75.3%) received HAART. BD were seen in 52 children, with the most frequent being genitourinary and cardiological. Anaemia in the first trimester was an associated risk for BD (17.9% vs. 8.1%, P = 0,04). Similarly, mothers who used any illicit drug (plus methadone), had a slightly higher risk for BD in their offspring (13.8% vs. 7.6%, P = 0,04) There was no increased risk for BD significantly associated with any of the in-utero used antiretrovirals, although Nevirapine use in-utero showed a protective effect. Children born to mothers who received ART in the first trimester had the same rate of BD (7.4%) as those whose mothers started ART in the second trimester (8.8%), P = 0,67., Conclusions: The proportion of BD that we have observed seems higher than those shown in other European teratogenicity studies and also higher than those shown in cohorts with HIV and antiretroviral exposed infants. This may be due to the fact that our series show the results of an active surveillance system (that includes ultrasound), where BD classically appear in a higher proportion. Immunovirological characteristics of the mother did not influence the proportion of BD, but anaemia in the fist trimester and the use of illicit drugs (or methadone) did. No specific antiretroviral drug was associated with an increase in BD, although Nevirapine showed a possible protective effect in the statistical analysis. Mothers who started antiretrovirals in the first trimester do not have more BD in their offspring than mothers who started on antiretrovirals later on.

Introduction: Mother-to-child HIV transmission is currently around 1% in western countries, due to prevention measures. Antiretroviral drugs do have adverse effects, anaemia and myelosupression caused by AZT being the most observed effects. In the present study, we analyse the prevalence of anaemia and neutropenia in an uninfected children cohort born to HIV-infected women., Material and Methods: We followed up 623 uninfected children belonging to the FIPSE cohort according to standardised protocols. This cohort groups 8 hospitals from Madrid and follows up HIV infected pregnant women and their children. Anaemia and neutropenia were defined according to the ACTG (AIDS Clinical Trails Group) toxicity tables. Children were classified according to prematurity, ethnic origin, birth weight, withdrawal syndrome, in-utero treatment and neonatal prophylaxis. Categorical variables were compared with the chi2 or the Fisher tests., Results: Anaemia was observed in 188 (30.1%) children during follow-up and 161 (25.8%) had anaemia grade 2 or higher. Prematurity (p < 0.001), low birth weight (p = 0.005) and Highly Active Antiretroviral Treatment (HAART) with Protease Inhibitors (p = 0.016) were associated with higher percentages of anaemia in children. Nadir haemoglobin values were reached by 6 weeks of life and anaemia was transient and disappeared by six months of age. Neutropenia was present in 41.9% (261 children) and 22.7% of the children had moderate-severe neutropenia. Prematurity was again associated with neutropenia (p = 0.01) and low birth weigh was associated only with moderate-severe neutropenia (p = 0.023). African infants had a higher percentage of neutropenia than the rest of the children (50% vs. 44%), although the differences were not significant. The type of in-utero treatment did not appear to influence the neutropenia. Neutropenia was still present in 12.5% of infants at 18 months of age. The type of neonatal prophylaxis to prevent mother-to-child transmission (monotherapy, dual therapy or triple therapy) did not influence either cytopenia., Conclusion: In our series, the proportion of children with anaemia is high: 30.1% Prematurity, low birth weight and HAART with IP were associated with a higher proportion of anaemia, which was transient and had little clinical relevance. The proportion of children with neutropenia was higher (41.9%) and was associated with prematurity, low birth weight and African origin. The type of neonatal prophylaxis does not seem to influence the development of cytopenias. Persistence of neutropenia (without clinical significance) was observed in a small percentage of the children 12.5%, at 18 months of age.

Objectives: We undertook a prospective study to estimate the prevalence of gestational diabetes mellitus (GDM) and associated risk factors in a cohort of 669 HIV-1 infected women., Methods: The O'Sullivan and glucose tolerance tests were performed during regular visits of 609 mothers., Results: The median age of the cohort was 30.7 years (range 16-44), with most women having had heterosexual contact (67%). The majority were in Centers for Disease Control (CDC) category A (71%) and 53% exhibited hepatitis C co-infection. Median viral load and CD4 count at third trimester were 545 cells/microL (range 139-1690 cells/microL) and 1.9 log (range 1.7-5.4), respectively. Seventy-four per cent of the patients were treated with highly active antiretroviral therapy (HAART), of whom 41% received a protease inhibitor (PI). An above-average prevalence of 7% [95% confidence interval (CI) 5.2-9.5] for positive GDM diagnosis was found. Risk factors associated with GDM in univariate analysis included older age, hepatitis C co-infection, stavudine and PI exposure. However, only older age [adjusted odds ratio (AOR) 1.09, 95% CI 1-1.1] and PI exposure (AOR 2.4, 95% CI 1-5.3) remained as independent risk factors for GDM development in multivariate analysis., Conclusions: In our cohort, the prevalence of GDM appears to be increased, with older age and PI exposure contributing as significant independent risk factors.

Introduction: Shigella spp. is a bacterium that frequently causes diarrhoea in underdeveloped countries, but not so much in Spain, where it has been published that its incidence has decreased in the last few years., Objective: The aim of this study has been to asses changes in the epidemiology of Shigella spp. infection over the last 5 years in children of Getafe, as well as the subspecies of Shigella spp. that cause illness in this area (area 10, Madrid), the need for hospitalisation, the complications and the treatment., Method: A retrospective study was carried out, based on a review of the medical charts of children less than fifteen years old and had a diagnosis of Shigella spp. infection during 2000-2006. They were identified through the Getafe Hospital Microbiology Service., Results: Nineteen patients were identified, of which only four needed to be hospitalised. There were no differences between males and females. The Shigella spp. subspecies identified were S. sonnei and S. flexneri. The most frequent symptoms were vomiting, abdominal pain, diarrhoea, and fever. Only one had dehydration as a complication. The treatment was symptomatic, except in the four hospitalised patients, who required fluid therapy and antibiotics. The outcome was good in all patients., Conclusion: In this study, there appears to be an increase in the Shigella spp. incidence over the last few years in Area 10 of Madrid. Due to the fact that Shigella spp. is not a frequent bacterium in Spain, there are not enough studies on it, therefore it would be of interest to carry out prospective studies, in order to confirm this increase in incidence.

Introduction: Despite the success of preventive measures against mother-to-child transmission (MTCT) of human immunodeficiency virus-1 and -2 (HIV-1 and -2) in developed countries, HIV-infected infants continue to be born. The aim of this study was to evaluate failures in the prevention of MTCT and the clinical characteristics of infected infants., Methods: The Foundation for the Investigation and Prevention of AIDS in Spain (FIPSE) Cohort in Madrid prospectively follows up children at risk of MTCT HIV born in eight public hospitals in Madrid. From May 2000 to December 2005, 632 children born to HIV-infected mothers were evaluated. Data from pregnancy follow-up, antiretroviral therapy (ART), and symptoms at diagnosis in infected infants were analyzed., Results: Nine infants were infected. The rate of vertical transmission was 1.42 (95% CI 0.7-2.68). Of the nine mothers, seven had not received ART during pregnancy (and five had not received ART at delivery). Of the mothers who received ART, one had only done so for the last month of pregnancy. Two infants were given three drugs as prevention of MTCT, one received bitherapy and six received monotherapy. The median age at diagnosis was 2.4 months (range 7 days-2 years). The mean plasma viral load at diagnosis was 276,000 copies/ml (range: 11,900-1,000,000). Five of the infants were symptomatic at diagnosis (P. jirovaci pneumonia in two, sepsis in one, recurrent bacterial infections in one, hepatosplenomegaly in one). Four of the nine infants had been admitted to hospital prior to HIV diagnosis., Discussion: Missed opportunities for the prevention of MTCT were identified in eight of the nine HIV-infected infants (89%). Administration of AZT during labor in HIV-infected mothers and triple therapy for the prevention of MTCT in high risk infants is not universal. Hospital admission in young infants at risk might lead to suspicion of infection in infants born to HIV-infected mothers. Improved implementation of all the preventive measures for MTCT should be encouraged.

Since the implementation of highly active antiretroviral therapy in HIV-infected children, response to scheduled vaccines may determinate future morbidity and mortality. The aims of this study have been to describe the current vaccine coverage, vaccine safety and concordance with vaccine recommendations of the 68 HIV-infected children and adolescents followed up in our Unit. Forty-four percent of the children received at least one dose of the oral polio vaccine (OPV). Only 9.1% needed and received a second set of hepatitis B virus immunization because of low vaccine response. Only 14.7% were vaccinated against varicella. Coverages of 82.3% and 100% have been reached with the 23-valent and the 7-valent pneumococcal vaccines, respectively. Meningococcal conjugated vaccine uptake was moderate (80.8%). Influenza annual vaccination coverage was poor: only 22.7% had well-documented yearly vaccines. In our experience, vaccine coverage is lower in those vaccines administered in primary care centres compared with the immunizations given at the hospital. OPV administration did not cause any adverse effect in the children or in their families. Vaccine coverage in HIV-infected children was suboptimal.

Background: Cytomegalovirus (CMV) is one of the most common opportunistic infections in AIDS patients. The aim of this study was to assess the influence of CMV infection in the first year of life and its the impact on survival and progression of the disease., Material/methods: This prospective cohort study included all children with a diagnosis of HIV infection in the first year of life followed at the University Hospital 12 de Octubre, Madrid. Urine culture was performed at birth or as soon as the diagnosis of HIV was given., Results: Among the 81 patients studied, 16 presented a positive culture for CMV in urine during the first year of life. At 2 and 5 years of age, 23.6% and 39.6% of the children, respectively, died among those children without CMV infection, whereas 20% and 40% of children with acquired CMV died at this time point. Neither a greater progression of the disease nor any differences in the degree of immunosupression were observed among the children infected with CMV compared with those not infected., Conclusions: In this study no relationships between CMV infection during the first year of life and faster progression of HIV infection or lower survival or a greater degree of immunosuppression in HIV-infected children was observed.

Background and Objective: The main strategies to avoid the vertical transmission of human immunodeficiency virus (HIV-1) is antiretroviral treatment during pregnancy, delivery and to the newborn. Nevertheless, there are scant data about safety of antiretroviral drugs and follow-up studies with a large number of pregnant women are needed. The aims of our study are: to assess toxicity associated with antiretroviral treatment, to determine vertical transmission, and to define epidemiological trends within this population. In this paper we present maternal characteristics of the cohort., Patients and Method: Observational, multicentric, collaborative study about an HIV-1 infected pregnant women cohort and their offspring (666 and 686 cases, respectively) who were born during the study period (from January or May 2000 to 31st december 2003)., Results: Most pregnant women were infected by heterosexual transmission (54%). 71% women were included in stage A of the Centers for Disease Control classification of HIV infection and 74% women have received high activity antiretroviral treatment during pregnancy. Prevalence of adverse effects treatment-related was 7%, mainly anaemia related to treatment with zidovudine. We found 6 cases of vertical transmission among 686 newborns (0.8%; 95% confidence interval, 0.3-1.8)., Conclusions: Most patients received highly active antiretroviral treatment, with a good tolerance and a low prevalence of adverse effects related to the treatment. Vertical transmission rate is very low, not higher than 1%. Apart from this, is necessary to pay attention to other phenomena like hepatitis C virus coinfection, other potentially serious adverse effects like hepatotoxicity and pregnancy-related pathologies more frequent in this population, like prematurity and gestational diabetes.

Introduction: In the last few years, the immigrant population in Spain, as well as the number of HIV-infected patients from countries where the prevalence of HIV-1 infection is higher, have continued to increase. No data are available on the impact of immigration on new cases of HIV-1 diagnosed in children. The objective of this study was to assess the clinical characteristics and determine the epidemiological trend of new diagnoses of pediatric HIV infection in Madrid in the last 8 years., Patients and Methods: We performed a retrospective study through review of the medical records of children in whom a new diagnosis HIV-1 infection was made in nine hospitals in the Autonomous Community of Madrid from 1997 to 2004. Two periods were compared: before December 2000 (period A) and after December 2000 (period B). Children born outside Spain or those whose parents had arrived in Spain in the previous 10 years were considered immigrants., Results: During the period analyzed, 97 children with HIV infection were identified and transmission was vertical in 93. Overall, 33 (34%) were immigrants (51% from Latin America, 27% from sub-Saharan Africa, 15% from the Maghreb, and 6% from Eastern Europe). The percentage of immigrant children increased from 26% (19/72) in period A to 56% (14/25) in period B (p: 0.013). The mean age at diagnosis was 3.9 +/- 0.8 years in the immigrant group and 3.7 +/- 0.5 in the group of Spanish children (p > 0.05). No differences were found in the type of transmission, CDC-clinical class, viral load or CD4 cells between Spanish and immigrant children., Conclusions: The proportion of immigrant children with HIV-1 infection is increasing in Madrid. In our experience, we found no significant differences in clinical or immunological category between immigrant and Spanish children with regard to diagnosis of HIV infection.

Chronic recurrent multifocal osteomyelitis is a rare disease of unknown etiology that mainly affects children. We present a retrospective review of the medical records of five patients with a diagnosis of chronic recurrent multifocal osteomyelitis in an infectious diseases clinic at a tertiary center. We describe the epidemiological, clinical and radiological features, laboratory, microbiological and histological findings, treatment, course and prognosis in these patients. There is no specific treatment for chronic recurrent multifocal osteomyelitis. There are new treatment options such the combination of azithromycin and calcitonin in children without clinical improvement with non-steroidal anti-inflammatory drugs.

Compulsive neuropsychiatric disorders are common in children and the most frequent is Gilles de la Tourette syndrome. Recently, a new disease has been described: the PANDAS syndrome (pediatric autoimmune neuropsychiatric disorders associated with streptococci). The etiology of this syndrome is uncertain but it has been associated with recent group A streptococcal infection (GAS). After an episode of pharyngitis, a boy aged 3 years and 9 months showed abrupt onset of a variety of neurobehavioral problems such as tics (consisting of elevation of the head and ipsilateral shoulder, winking, and grimaces) and compulsions (such as repeatedly hitting objects). A complete biochemical study was performed, including Cu and ceruloplasmin (which had normal values), antistreptolysin O (ASLO) and anti-DNAse (showing elevated values). Pharyngeal culture revealed GAS. The child was initially treated with valproic acid, but his subsequent improvement coincided with penicillin treatment for 10 days. Three months afterwards, ASLO values were reduced and at the 6-month follow-up the improvement was maintained even after suspension of valproic acid. Immunohistochemical studies were requested. PANDAS syndrome was first described in 1998 in a group of children who presented 1) obsessive compulsive disorders and/or tics, 2) episodic course with abrupt exacerbations, 3) abnormal results of neurologic examination (choreiform movements), and 4) temporal relation between GAS infection and onset of symptoms. The etiology of this syndrome is unclear, and it has been postulated that certain streptococcal antigens trigger antibodies which, through a process of molecular mimicry, cross-react with epitopes on the basal ganglia of susceptible hosts, such as the B8/17 antigen, among others. Current recommendations include penicillin treatment of each exacerbation with positive throat culture, and more aggressive therapies (intravenous immunoglobulin or plasmapheresis) when symptoms are severe. We believe that the case presented herein is a probable PANDAS syndrome, which would be the first case described in Spain.

Background: In recent years, lymphadenitis caused by atypical mycobacteria (also called nontuberculous mycobacteria [NTMB] or, more recently, environmental) have played a significant role in the differential diagnosis of adenitis in non-immunocompromised children., Objectives: To describe the clinical and pathological findings in childhood NTMB adenitis and study the possible usefulness of antimicrobial therapy in addition to surgery., Methods: We present eight cases of neck lymphadenitis occurring over a 5-year period. All of the children received combined chemotherapy, and six also underwent surgery. Of the two remaining patients, the parents of one child refused surgery and a watchful approach was adopted in the other., Results: Complete clinical recovery was achieved in all patients except one who did not undergo surgery., Conclusions: Prolonged administration of two antibiotics (of which one must be clarithromycin) in addition to surgery was well-tolerated and could be useful in patients with NTMB neck lymphadenitis.

Introduction: Spondylodiscitis is a relatively uncommon entity in infancy and childhood, with typical, although non-specific symptoms. The aim of this study was to describe the clinical features at presentation and follow-up in patients diagnosed with spondylodiscitis in hospitals in the Autonomous Community of Madrid., Patients and Methods: All cases of spondylodiscitis diagnosed in children in the hospitals of La Paz, Niño Jesús, Gregorio Marañón, Severo Ochoa, Doce de Octubre and Getafe in Madrid were reviewed. Their clinical features, diagnostic tests, treatment and follow-up were analyzed., Results: Twenty children with a mean age of 37 months were studied. The level of disc involvement was L5-S1 in six patients, L2-L3 in five, L3-L4 in four, C6-C7 in two, and D12-L1 in one. The mean time before diagnosis was 20 +/- 16 days. The most frequent symptoms were gait disturbances, limping, or inability to remain seated. Eleven patients had low grade fever (< 38.5 degrees C). Other less specific symptoms were irritability, constipation and abdominal pain. All patients presented moderate leukocytosis without neutrophilia. The mean erythrocyte sedimentation rate was 60 +/- 26. The most frequently used diagnostic tests were conventional spine radiographs, technetium-99m bone scan and magnetic resonance imaging. All patients received antibiotics; three received oral antibiotics only and the remaining patients received intravenous and oral antibiotics. The most frequently prescribed antibiotics were cefuroxime, cloxacillin and amoxicillin-clavulanate. The duration of treatment ranged between 3 and 8 weeks. All patients had a favorable outcome, although in eight, radiological sequelae were observed., Conclusions: Spondylodiscitis is not exceptional in childhood and awareness of this entity among pediatricians should be increased.

Background: Cytomegalovirus (CMV) is the most common congenital viral infection, mainly in the infants of HIV-infected women. The aim of this study was to evaluate the prevalence of congenital CMV infection in infants born to HIV-infected women in our hospital, the possible influence of maternal antiretroviral therapy, the relationship between vertical HIV transmission and congenital CMV infection, and the clinical outcome of these infants., Patients and Methods: Between 1987 and 2003, we performed a prospective, cohort study of all the infants born to HIV-infected mothers, in whom CMV was cultured in urine in the neonatal period. Congenital CMV infection was defined as a CMV positive urine culture obtained in the first 3 weeks of life., Results: A total of 257 patients were included in the study, with positive CMV urine culture in 12 (4.6 %). Before 1997 the prevalence was 9.2 % vs 1.34 % in the second period (p < 0.01). In infants born to HIV-infected women without zidovudine therapy the prevalence was 6.3 % compared with 3.1 % in the group with zidovudine therapy (p > 0.05). Vertical HIV transmission was observed in 23 infants, of which six (26 %) had congenital CMV coinfection. Only six infants (2.5 %) without HIV-infection had congenital CMV infection (p < 0.01). The outcome of congenital CMV infection was good in all infants., Conclusions: Congenital CMV infection is more frequent in infants born to HIV-infected women. The prevalence was higher in the first study period and in infants with vertical HIV transmission. All infants with congenital CMV infection had a favorable outcome.

Introduction: There are few cross-sectional studies describing the current situation of HIV-1-infected children. Such studies would be useful to determine patients' clinical and immunologic and virologic status, currently prescribed therapies and their associated toxicity., Objectives: To perform a descriptive analysis of the clinical, immunological and virological status of HIV-1-infected children followed-up in the pediatric unit of a tertiary hospital and describe the current antiretroviral therapies used to treat them., Material and Methods: A cross-sectional study was performed. Data were collected from all HIV-1-infected children followed-up until January 2002 in a large pediatric referral hospital (Hospital 12 de Octubre in Madrid). Clinical evaluation and laboratory investigations were scheduled to be performed every 3 months. The most recent CD4 and plasma viral loads were evaluated. Viral loads were considered undetectable when there were less than 300 copies/ml at the last evaluation., Results: Sixty-six HIV-1-infected children who were followed-up to January 2002 were analyzed. All the children acquired the infection through vertical transmission except one, in whom the mode of transmission was unknown. The median age was 111 months (18-216). Twenty children were category C. The median CD4 cell count was 953 cells/mm3 (276-3137), 28 % +/- 8 (12.42). One child was receiving no therapy, four were on combination therapy with two nucleoside reverse transcriptase inhibitors (NRTI) and 61 were receiving highly active anti-retroviral therapy (HAART). Twenty-seven children (44 %) were receiving the first HAART regimen, 23 the second, and 11 had already been switched more than twice. Overall, 37 of the 61 patients receiving HAART had an undetectable plasma viral load., Conclusions: Most children in our study had gone through several antiretroviral regimens, although not all children were being treated with HAART. Fifty-six percent of the patients with HAART had an undetectable plasma viral load. However, new complications associated with this therapy have begun to appear.

Introduction: Since the introduction of zidovudine, perinatal transmission (PT) of HIV-1 has markedly decreased, although a transmission rate of zero has still not been achieved. The present study describes the trend in PT over 13 years, as well as changes in medical-surgical management and their influence on PT., Patients and Methods: We performed a prospective cohort study of all HIV-1-infected mother-infant pairs born between January 1987 and December 1999 in Hospital 12 Octubre in Madrid. Univariate analysis was performed to determine the relationship between possible risk factors and PT., Results: A total of 290 mothers and 291 children were included. Thirty-eight children were infected, 28 of these before 1994 (PT rate: 13 %). There were no cases of infection when the full ACTG 076 protocol was implemented. Factors significantly associated with a higher transmission rate were prolonged rupture of membranes and nonelective caesarean section. The main protective factor was antiretroviral therapy., Conclusions: PT markedly decreased after the introduction of the ACTG 076 protocol. In the last 13 years, maternal age and maternal infection due to heterosexual transmission have increased. Other changes observed were modifications in obstetric interventions and the generalized use of zidovudine and antiretroviral therapy during pregnancy.

In recent years, major advances have been made in the care of HIV-infected children, particularly in antiretroviral treatment, which have dramatically improved survival and quality of life. The goal of highly active antiretroviral therapy (HAART), which includes at least three potent drugs, is the maximal and most durable suppression of viral replication possible, which is often not achieved despite clear immunologic and clinical improvement. There are still major barriers to achieving this goal, mainly the difficulty of permanent adherence to complex regimens and treatment-related toxicities. Adverse events are frequent, including a high prevalence of metabolic complications with unknown consequences in the future. These drawbacks of antiretroviral treatment are leading to a more conservative initial approach, as well as to research into simpler and less toxic therapeutic options. New strategies should continue to be developed to overcome the still important limitations of current antiretroviral treatment.