Epidemiology and clinical features of Streptococcus pyogenes bloodstream infections in children in Madrid, Spain.

Studies have shown increased invasive Group A Streptococcus (GAS) disease, including bloodstream infections (GAS-BSI). However, the epidemiological data of GAS-BSI are limited in children. We aimed to describe GAS-BSI in children in Madrid, over 13 years (2005-2017). Multicenter retrospective cohort study from 16 hospitals from Madrid, Spain. Epidemiology, symptomatology, laboratory, treatment, and outcome of GAS-BSI in children ≤ 16 years were analyzed. 109 cases of GAS-BSI were included, with incidence rate of 4.3 episodes/100,000 children attended at the emergency department/year. We compared incidence between two periods (P1: 2005-June 2011 vs P2: July 2011-2017) and observed a non-significant increase along the study period (annual percentage change: + 6.0% [95%CI: -2.7, + 15.4]; p = 0.163). Median age was 24.1 months (IQR: 14.0-53.7), peaking during the first four years of life (89/109 cases; 81.6%). Primary BSI (46.8%), skin and soft tissue (21.1%), and osteoarticular infections (18.3%) were the most common syndromes. We compared children with primary BSI with those with a known source and observed that the former had shorter hospital stay (7 vs. 13 days; p = 0.003) and received intravenous antibiotics less frequently (72.5% vs. 94.8%; p = 0.001) and for shorter duration of total antibiotic therapy (10 vs. 21 days; p = 0.001). 22% of cases required PICU admission. Factors associated with severity were respiratory distress, pneumonia, thrombocytopenia, and surgery, but in multivariate analysis, only respiratory distress remained significant (adjusted OR:9.23 [95%CI: 2.16-29.41]). Two children (1.8%) died.   Conclusion: We observed an increasing, although non-significant, trend of GAS-BSI incidence within the study. Younger children were more frequently involved, and primary BSI was the most common and less severe syndrome. PICU admission was frequent, being respiratory distress the main risk factor. What is known: • In recent decades, several reports have shown a worldwide increase in the incidence of invasive Group A streptococcal disease (GAS), including bloodstream infection (BSI). Recently, there have been a few reports showing an increase in severity as well. • There needs to be more information on the epidemiology in children since most studies predominantly include adults. What is new: • This study, carried out in children with GAS-BSI in Madrid, shows that GAS-BSI affects mostly younger children, with a broad spectrum of manifestations, needing PICU admission frequently. Respiratory distress was the leading risk factor for severity, whereas primary BSI seemed to be less severe. • We observed an increasing, although non-significant, trend of GAS-BSI incidence in recent years (2005-2017).

Cytomegalovirus DNA Detection by Polymerase Chain Reaction in Cerebrospinal Fluid of Infants With Congenital Infection: Associations With Clinical Evaluation at Birth and Implications for Follow-up.

BACKGROUND: DNA detection of human cytomegalovirus (hCMV) in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) is a marker of central nervous system (CNS) involvement in congenital hCMV infection (cCMV), but its prognostic value is unknown. METHODS: A multicenter, retrospective study was performed using the Spanish Congenital Cytomegalovirus Infection Database (REDICCMV; http://www.cmvcongenito.es). Newborns with cCMV and a lumbar puncture performed were included and classified according to their hCMV-PCR in CSF result (positive/negative). Clinical characteristics, neuroimaging abnormalities, plasma viral load, and audiological and neurological outcomes of both groups were compared. RESULTS: A total of 136 neonates were included in the study: 21 (15.4%) with positive CSF hCMV-PCR and 115 (84.6%) with negative results. Seventeen patients (81%) in the positive group were symptomatic at birth compared with 52.2% of infants in the negative group (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.28-14.1; P = .01). Only 4 asymptomatic newborns (6.8%) had a positive CSF hCMV-PCR. There were no differences between groups regarding the rate of microcephaly, neuroimaging abnormalities, neurological sequelae at 6 months of age, or plasma viral load. Sensorineural hearing loss (SNHL) at birth was associated with a positive CSF hCMV-PCR result (OR, 3.49; 95% CI, 1.08-11.27; P = .04), although no association was found at 6 months of age. CONCLUSIONS: A positive hCMV-PCR result in CSF is associated with symptomatic cCMV and SNHL at birth. However, no differences in neuroimaging studies, plasma viral load, or outcomes at 6 months were found. These results suggest that hCMV-PCR in CSF may not be a useful prognostic marker in cCMV.

Drug utilization and off-label drug use in Spanish pediatric gastroenterology outpatients.

BACKGROUND AND OBJECTIVES: The clinical use of medicines outside the conditions authorized in their Summary of Product Characteristics (SPC) (off-label use) is a common practice in pediatrics. The aim of the present study was to describe and quantify the medicines received by children attended in the pediatric gastroenterology department, their off-label use, and compliance with accepted rules for said use. METHODS: A retrospective observational study was performed on all of the patients who had their first consultation in pediatric gastroenterology between January 1 and October 31, 2010. All of the clinical information and medicines prescribed were analyzed. Off-label use was defined as the use of medicines in indications not included in the officially approved SPC or in ages not included or recommended in the SPC as well as the use of doses, intervals, or administration routes different from those considered in the SPC. RESULTS: A total of 695 patients (52.8% male) were included, 48.2% younger than 2 years. Two-hundred seven patients (29.8%) received 331 prescriptions. The most commonly used medicines were anti-H2 and proton pump inhibitors. Of all the prescriptions, 33.2% were considered off-label, and up to 47.3% of the prescribed patients had at least 1 medicine under off-label conditions. The medical records contained no documentation on information given to the parents regarding off-label use. CONCLUSIONS: The study found a high percentage of off-label use of medicines in the Pediatric Gastroenterology outpatient setting, especially in children younger than 2 years. Several initiatives were derived from the present study and implemented in our hospital.

Tuberculin skin test in bacille Calmette-Guérin-vaccinated children: how should we interpret the results?

BACKGROUND: The tuberculin skin test (TST) is the most useful method for the diagnosis of tuberculosis (TB). There is no evidence about the effect of bacillus Calmette-Guerin (BCG) vaccine on the interpretation of TST results. OBJECTIVE: The aim of this study was to evaluate TST results in a population of immigrants and adopted children, analyzing the effect of the vaccine on TST. METHODS: Cross-sectional observational study including immigrants or adopted children evaluated in our unit between January 2003 and December 2008 was made. Children diagnosed with TB, live attenuated virus vaccinated 2 months earlier, HIV-infected, chronically ill, or under treatment with immunosuppressive agents were excluded. TST was considered the dependent variable. Independent variables were gender, age, geographical origin, BCG scar, nutritional status, immune status, and intestinal parasites infestation. RESULTS: One thousand seventy-four children were included, 69.6 % are female; their origin includes China (34.7 %), Latin America (20.8 %), India/Nepal (19.4 %), Eastern Europe (15.7 %), and Africa (9.3 %). BCG scar was present in 79 % of children. Mantoux = 0 mm in 84.4 %, <10 mm in 4.1 %, and ≥10 mm in 11.4 %. Only two variables, age and BCG scar, influenced TST result. Risk of a TST false-positive due to BCG disappears 3 years after vaccine administration. CONCLUSIONS: A history of BCG vaccination at birth does not interfere with TST results in children >3 years old. Under 3 years of age, BCG does interfere with and may cause a false-positive TST result. In these cases, the use of interferon-gamma release assays (IGRAs) is recommended. If IGRAs are not available or when results are indeterminate, ignoring the antecedent of the vaccine is recommended.

Pediatric Chagas disease in the non-endemic area of Madrid: A fifteen-year review (2004-2018).

BACKGROUND: Chagas disease (CD) has become an emerging global health problem in association with the immigration of individuals from endemic areas (in LatinAmerica) to other countries.Spain is the country in Europe with the highest number of CD cases. Concerning pediatric CD, treatment is not only better tolerated by younger children but also has greater cure possibilities. The aim of this study was to describe clinical and epidemiological aspects of CD in a pediatric population diagnosed of 10 hospitals in the Community of Madrid during the 2004-2018 period, as well as the safety and efficacy of CD treatment on this population. METHODOLOGY/PRINCIPAL FINDINGS: A multicenter, retrospective, descriptive study was conducted. The studied population included all identified children under the age of 18 with a diagnosis of CD. Diagnosis was performed with a positive parasitological test (with subsequent confirmation) or confirmed persistence of positive serology beyond 9 months, for children younger than one year-old, and with two different positive serological tests, for children older than one. Fifty-one children were included (59% male; 50.9% born in Spain). All mothers were from Latin America. The median age at diagnosis was 0.7 months for those under one year of age, and 11.08 years for those older than one year-old. Only one case presented a symptomatic course (hydrops faetalis, haemodynamic instability at birth, ascites, anaemia). For 94% treatment was completed. Considering patients who received benznidazole (47), AE were recorded in 48,9%. Among the 32 patients older than one year-old treated with benznidazole, 18 (56.25%) had adverse events whereas in the 15 under one year, 5(33,3%) did. Eigtheen (78.2%) of the patients with benznidazole AE were older than one year-old(median age 11.4 years). Of the patients treated with nifurtimox (9), AE were reported in 3 cases (33,3%). Cure was confirmed in 80% of the children under one year-old vs 4.3% in those older (p<0.001). Loss to follow- up occurred in 35.3% of patients. CONCLUSIONS/SIGNIFICANCES: Screening programs of CD since birth allow early diagnosis and treatment, with a significantly higher cure rate in children treated before one year of age, with lower incidence of adverse events. The high proportion of patients lost to follow-up in this vulnerable population is of concern.

Duration of immunity to measles, rubella and mumps during the first year of life.

INTRODUCTION AND OBJECTIVES: The MMR vaccine was included in the official vaccination schedule in Spain in 1981. Currently, most women of childbearing age are vaccinated and have not been naturally infected. Several studies have shown that vaccinated women have a lower antibody concentration than that achieved after natural infection, and a shorter duration of transplacentally acquired antibodies in their children. The objective of this study was to determine the antibody titer in mothers and their infants at birth and throughout the first year of life under current epidemiological circumstances. MATERIAL AND METHODS: Single-center, observational, descriptive and prospective study conducted between October 2013 and December 2014. One sample of serum and another of a dried blood spot on filter paper were taken from each mother. Dried blood spot samples on filter paper were taken from the children at birth, and at 3, 6, 9 and 12 months. In all the samples, levels of antibodies to the measles, rubella and mumps viruses were measured using standardized quantitative assays. RESULTS: 146 mother-child pairs were included. 78.4%, 86.9% and 67.1% of mothers had antibodies to measles, rubella and mumps, respectively. A decrease in the antibody titer in children was observed after 3 months, and no antibodies against the three diseases were detected by the age of 6 months. Comparisons revealed no statistically significant differences between the antibody titers of children of mothers born before or after 1981 during the first year of their life. DISCUSSION: The rapid loss of transplacentally acquired antibodies against measles, rubella and mumps, under current epidemiological conditions, suggests that bringing the MMR vaccination forward to 9 months might be justified. Larger population studies are needed to confirm these results.

Effect of nutritional status on Tuberculin skin testing.

OBJECTIVES: To evaluate Tuberculin skin test (TST) results in a population of immigrants and internationally adopted children from several geographical areas; to analyze whether nutritional status can modify TST results. METHODS: This cross-sectional observational study included adopted children and immigrants evaluated in the authors' unit between January 2003 and December 2008. Children diagnosed with tuberculosis, or vaccinated with live attenuated virus 2 mo earlier, HIV-infected, chronically ill or under treatment with immunosuppressive agents were excluded. TST was considered as dependent variable. Independent variables were gender, age, geographical origin, BCG scar, nutritional status, immune status and intestinal parasitism. RESULTS: One thousand seventy four children were included; 69.6 % were girls. There was a BCG scar in 79 % of children. Mantoux = 0 mm was found in 84.4 %, <10 mm in 4.1 %, and ≥10 mm in 11.4 % of children. Nutrition (McLaren's classification) was normal (≥90 %) in 26.7 % of the subjects, with mild malnutrition (80-89 %) in 36 %, moderate (70-79 %) in 23.2 % and severe (≤69 %) in 14.1 %. There was no difference in TST results among different nutritional status children. CONCLUSIONS: The nutritional status, measured by McLaren's classification, does not changes the results of TST. McLaren's classification only grades protein-caloric malnutrition, so in authors' experience this type of malnutrition does not interfere with TST results. Implementing other nutritional parameters could help to determine whether nutritional status should be taken into account when interpreting TST results.

Oseltamivir treatment for influenza in hospitalized children without underlying diseases.

AIM: To determine whether the treatment with oseltamivir improves the outcome of children with confirmed influenza infection and no other underlying disease. METHODS: Multicentric, retrospective study performed in 10 hospitals of Madrid between September 2010 and June 2012. All children admitted to the hospitals with confirmed influenza infections were eligible. Children with risk factors for serious disease and nosocomial influenza infections were excluded. Asthma was not considered an exclusion factor. The study compared patients treated and untreated with oseltamivir. Fever duration, oxygen support, antibiotics administration, length of hospital stay, intensive care admission and bacterial complications were analyzed. To compare variables, χ(2) test, Fisher exact test, ANOVA or Mann-Whitney U test were used. RESULTS: Two hundred eighty-seven children were included and 93 of them were treated with oseltamivir (32%). There were no significant differences between treated and untreated patients in days of fever after admission (1.7 ± 2; 2.1 ± 2.9, P > 0.05), length of stay (5.2 ± 3.6; 5.5 ± 3.4, P > 0.05), days of hypoxia (1.6 ± 2.3; 2.1 ± 2.9, P > 0.05), diagnosis of bacterial pneumonia (10%; 17%, P > 0.05), intensive care admission (6.5%; 1.5%,P > 0.05) or antibiotic prescription (44%; 51%, P > 0.05). There were no differences when the population was stratified by age (below or over 1 year) or by the presence or absence of asthma. CONCLUSIONS: There were no proven benefits of treatment with oseltamivir in hospitalized pediatric patients without the underlying diseases or risk factors for developing a serious illness, including those with asthma.

[Prevalence of antibodies against hepatitis A and B in HIV-1-infected children and adolescents]. / Anticuerpos anti-VHB y VHA en niños y adolescentes con VIH.

INTRODUCTION: Patients coinfected with HIV and hepatitis B virus (HBV) have a higher risk of developing chronic HBV infection and a higher risk of hepatotoxicity. Hepatitis A virus (HAV) in HIV-infected patients may require antiretroviral treatment interruption, producing prolonged viremia. In this study, we assess the prevalence of protective antibodies in these patients. METHODS: A cross-sectional study was conducted to determine the prevalence of IgG antibodies against HAV and antibody against HBs (anti-HBs) in a cohort of 121 HIV-infected children and adolescents (1-19 years), followed-up in 4 public hospitals in Madrid (Spain). RESULTS: Among the total, 12.4% (95% CI: 7.1-19.6%) of children and adolescents had positive serology for HAV. Children of immigrant origin presented a higher percentage than children born in Spain: 50% vs. 6.2%, respectively (P<0.001). In addition, 16.5% (95% CI: 10.4-24.3) of the study population had protective anti-HBs. A higher percentage of children with anti-HBs antibodies was seen in CDC clinical category A: 20% vs. 16% of those in clinical category B vs. 9.4% of those in clinical category C (P=0.19). The percentage of positive-positive children progressively decreased according to the years elapsed since HBV vaccination. DISCUSSION: Most HIV-infected children and adolescents have no protective antibodies against natural infection by HBV and HAV. More studies are needed to define the best vaccination strategy to achieve a higher percentage of patients protected against these infections.

Anticuerpos anti-VHB y VHA en niños y adolescentes con VIH / Prevalence of antibodies against hepatitis A and B in HIV-1-infected children and adolescents

Introducción Los pacientes con virus de la inmunodeficiencia humana (VIH) coinfectados con virus de la hepatitis B (VHB) tienen mayor riesgo de desarrollo de hepatitis B crónica y de hepatotoxicidad con el tratamiento antirretrovírico (TAR). El desarrollo de hepatitis A en el paciente con VIH podría obligar a suspender el TAR y producir una viremia más prolongada. En este trabajo se pretende determinar la prevalencia de anticuerpos protectores. Métodos Se realizó un estudio transversal para establecer la prevalencia de anticuerpos inmunoglobulina G frente al virus de la hepatitis A (VHA) y de anticuerpos frente al antígeno de superficie del VHB (AcHBs) en una cohorte de 121 niños y adolescentes de 1 a 19 años infectados por VIH, de 4 hospitales públicos de Madrid. Resultados El 12,4% de los pacientes (IC [intervalo de confianza] del 95%: 7,1 al 9,6%) presentó serología positiva para VHA. Los niños de origen inmigrante tuvieron una mayor prevalencia (el 50 frente al 6,2% en los niños nacidos en España) (p<0,001). La proporción de niños con AcHBs positivos fue del 16,5% (IC del 95%: 10,4 al 4,3%). Hubo una mayor proporción de niños con anticuerpos protectores en el estadio A (20%) frente al B (16%) y al C (9,4%) (p = 0,19). Este porcentaje disminuía según el tiempo transcurrido desde la vacunación. Discusión La mayoría de los niños y adolescentes con VIH no presentan anticuerpos protectores frente a la infección natural por VHA y VHB. Es necesario plantear una estrategia de vacunación para conseguir una mayor proporción de pacientes protegidos frente a la hepatitis A y a la hepatitis B (AU)

Introduction Patients coinfected with HIV and hepatitis B virus (HBV) have a higher risk of developing chronic HBV infection and a higher risk of hepatotoxicity. Hepatitis A virus (HAV) in HIV-infected patients may require antiretroviral treatment interruption, producing prolonged viremia. In this study, we assess the prevalence of protective antibodies in these patients. Methods A cross-sectional study was conducted to determine the prevalence of IgG antibodies against HAV and antibody against HBs (anti-HBs) in a cohort of 121 HIV-infected children and adolescents (1–19 years), followed-up in 4 public hospitals in Madrid (Spain).Results Among the total, 12.4% (95% CI: 7.1–19.6%) of children and adolescents had positive serology for HAV. Children of immigrant origin presented a higher percentage than children born in Spain: 50% vs. 6.2%, respectively (P<0.001). In addition, 16.5% (95% CI: 10.4–24.3) of the study population had protective anti-HBs. A higher percentage of children with anti-HBs antibodies was seen in CDC clinical category A: 20% vs. 16% of those in clinical category B vs. 9.4% of those in clinical category C (P=0.19). The percentage of positive-positive children progressively decreased according to the years elapsed since HBV vaccination. Discussion Most HIV-infected children and adolescents have no protective antibodies against natural infection by HBV and HAV. More studies are needed to define the best vaccination strategy to achieve a higher percentage of patients protected against these infections (AU)