Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicenter experience.

Chronic granulomatous disease (CGD) can be cured by allogeneic hemopoietic stem cell transplantation (HSCT). Complications include graft failure, graft-versus-host disease (GVHD), infection, and transplant-related mortality; therefore, reduced-intensity conditioning regimens are being used to improve outcomes. In this retrospective study, the aim was to determine the outcome of treosulfan-based conditioning in HSCT for pediatric patients with CGD. The following data were collected: risk features pre-HSCT, additional conditioning agents, donor type and stem cell source, toxicity, engraftment, GVHD, chimerism, viral reactivation, post-HSCT complications, length of follow-up, and outcome. Seventy patients (median age, 107 months; interquartile range [IQR], 46-232 months) from 16 centers worldwide were transplanted between 2006 and 2015. Ninety-one percent had high-risk features. Fifty-seven HLA-matched donors, 12 HLA-mismatched donors, and 1 CD3(+)TCR αß/CD19 depleted parental haploidentical transplants were performed. No major toxicity was reported. Median times to neutrophil and platelet engraftment were 17 (IQR, 15-35) and 16 (IQR, 13-50) days. At a median follow-up of 34 months (IQR, 13-102 months), the overall survival was 91.4%, and event-free survival was 81.4%. The cumulative incidence of acute grade III-IV GVHD was 12%. Nine patients developed chronic GVHD. When split cell chimerism was available, 95% or more myeloid donor chimerism was documented in 80% of surviving patients. Secondary graft failure occurred in 12% of patients. Treosulfan-containing conditioning regimens can be used safely in HSCT for children with CGD and high-risk clinical features, achieving excellent survival with high myeloid chimerism. Further studies are needed to compare with other regimens and evaluate the long-term outcome, particularly on fertility.

Emerging (val)ganciclovir resistance during treatment of congenital CMV infection: a case report and review of the literature.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is an important illness that is a common cause of hearing loss in newborn infants and a major cause of disability in children. For that reason, treatment of symptomatic patients with either ganciclovir or its pro-drug valganciclovir is recommended. Treatment duration of 6 months has been shown to be more beneficial than shorter courses; however, there is uncertainty regarding emergence of resistance strains, secondary effects and long term sequelae. CASE PRESENTATION: Here we present a female infant with symptomatic cCMV who was treated from day 5 of life with oral valganciclovir. In spite of close monitoring of her drug levels and increments of her treatment dose according to weight gain, she developed ganciclovir resistance after 4 months of treatment, with increasing viraemia and petechiae. Adherence to treatment was assessed and felt to be good. Clinically, although she had marked developmental delay, she was making steady progress. In view of the development of resistance treatment was stopped at 5 months of age. No secondary effects of ganciclovir were noted during the whole course. CONCLUSIONS: There were few cases in the literature reporting resistance to ganciclovir for cCMV before the new recommendations for a 6 months treatment course for this infection were published. As demonstrated in our patient, surveillance with periodic viral loads and drug monitoring are vital to identify emerging resistance and optimise antiviral dosing according to weight gain.

COVID-19 clinical features in primary care: COVIDPAP study.

OBJECTIVES: In Spain, the tools to diagnose COVID-19 were available in primary care from May 2020. Previously most studies described inpatients or patients in A&E departments, and fever and cough were the most frequent symptoms. This study aims to define the clinical picture of the pediatric COVID-19 in the community. METHODS: A descriptive and analytical observational study was performed including pediatric cases (0-14years) from 255 pediatricians, proportionally distributed to its population, from primary health centers in Spain, from 12th May 2020 to 30th April 2021. Diagnostics were made by PCR detection of viral RNA, rapid antigen detection test or positive IgG serology. RESULTS: There were 10,021 positive children included, 48.4% women, mean age 8,04±4.17years. Infection was detected due to contact tracing (70.9%), compatible symptoms (18.8%). Household was the main source of transmission (64.9%), followed by school setting (10%) or unknown (9.9%). We did not find any significant differences in the incidence between holidays and school terms. 43.2% of the children were asymptomatic. Most frequent symptoms are rhinorrhea in <2years, fever in 3-8years and headache in >9years. An exhaustive description of objective and subjective symptoms by age is made. 18 patients were hospitalized, one with multisystem inflammatory syndrome in children. There were no deaths. CONCLUSIONS: pediatric COVID-19 is a mild disease, with a large number of asymptomatic cases, with very few hospital admissions and deaths. The main setting for transmission is the household, and school closures should be a last resource measure during the COVID-19 pandemic. A specific clinical picture of pediatric COVID-19 was not found.

[COVID-19 clinical features in primary care: COVIDPAP study]. / Expresión clínica de la COVID-19 en pediatría de atención primaria: estudio COVIDPAP.

Objectives: In Spain, the tools to diagnose COVID-19 were available in primary care from May 2020. Previously most studies described inpatients, and fever and cough were the most frequent symptoms. This study aims to define the clinical picture of the pediatric COVID-19 in the community. Methods: A descriptive and analytical observational study was performed including pediatric cases (0-14y) from 255 pediatricians, proportionally distributed to its population, from primary health centers in Spain, from 12th May 2020 to 30th April 2021. Diagnostics were made by PCR detection of viral RNA, rapid antigen detection test or positive IgG serology. Results: There were 10,021 positive children included, 48.4% women, mean age 8,04 ± 4.17 years. Infection was detected due to contact tracing (70.9%), compatible symptoms (18.8%). Household was the main source of transmission (64.9%), followed by school setting (10%) or unknown (9.9%). We did not find any significant differences in the incidence between holidays and school terms. 43.2% of the children were asymptomatic. Most frequent symptoms are rhinorrhea in < 2 y, fever in 3-8 y and headache in > 9 y. An exhaustive description of objective and subjective symptoms by age is made. 18 patients were hospitalized, one with multisystem inflammatory syndrome in children. There were no deaths. Conclusions: Pediatric COVID-19 is a mild disease, with a large number of asymptomatic cases, with very few hospital admissions and deaths. The main setting for transmission is the household, and school closures should be a last resource measure during the COVID-19 pandemic. A specific clinical picture of pediatric COVID-19 was not found.

[Epidemiology of nasopharyngeal carriage of Streptococcus pneumoniae in children < 6 years old in Seville]. / Epidemiología de la colonización nasofaríngea por Streptococcus pneumoniae en niños menores de 6 años de la ciudad de Sevilla.

INTRODUCTION: The aim of this investigation was to study the epidemiology of nasopharyngeal (NP) colonization with Streptococcus pneumoniae after the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7). METHODS: NP swabs were obtained from 848 children aged 6 months to six years seen in four primary care centres (healthy children) and in two emergency depeartments (sick children) from Seville. The study was conducted between February 2005 and June 2008. RESULTS: A total of 278 (33%) children carried S. pneumoniae. Pneumococcal colonization was independently predicted by school attendance or child care participation (OR 2.21; 95% CI 1.54- 3.15; P=.0001) and younger age. Recent antibiotic use was protective (OR 0.68; 95% CI 0.48-0.94; P=.02). PCV7 uptake was 41%. Risk of carriage of PCV7- type pneumococci was lower among children who had received ≥1 dose of PCV7 (7% vs 29%; [OR 0.21; 95% CI 0.09-0.49; P=.0001]). The proportion of pneumococcal isolates with oral penicillin non-susceptibility and amoxicillin resistance were 33% and 3%, respectively. Amoxicillin resistance in colonized children was associated with prior antibiotic usage (OR 4.29; 95% CI 1.09-20.02). CONCLUSIONS: NP colonization rates with PCV7- type pneumococci were low compared to those found in studies prior to PCV7 introduction, both in vaccinated and unvaccinated subjects. Factors related to age and overcrowding increased the prevalence of pneumococcal carriage. Use of antibiotics reduced the overall carriage of pneumococci, but was a risk factor for colonization with amoxicillin resistant pneumococci.

Expresión clínica de la COVID-19 en pediatría de atención primaria: estudio COVIDPAP / COVID-19 clinical features in primary care: COVIDPAP study

Objetivos: En España, las pruebas diagnósticas de COVID-19 en atención primaria estuvieron disponibles desde mayo de 2020. Previamente la mayoría de los estudios describían pacientes hospitalarios: la fiebre y la tos eran los síntomas más frecuentes. Interesaba conocer la expresión clínica de la COVID-19 pediátrica en la comunidad. Métodos: Estudio descriptivo analítico observacional de casos pediátricos (0-14 años) de 255 pediatras de atención primaria españoles, del 12/5/2020 al 30/4/2021. Los diagnósticos se determinaron por PCR, test rápido de detección de antígeno o serología IgG positiva. Resultados: Se incluyeron 10.021 niños, 48,4% mujeres, con una edad media de 8,04±4,17 años. Se detectó la infección por búsqueda de contactos (70,9%) o síntomas compatibles (18,8%). El hogar familiar fue la principal fuente de contagio (64,9%), seguido por los colegios (10%) o de origen desconocido (9,9%). No hubo diferencias significativas en la incidencia entre temporadas vacacionales o lectivas. El 43,2% fueron asintomáticos. Los síntomas más frecuentemente encontrados fueron rinorrea en menores de 2 años, fiebre entre 3 y 8 años y cefalea en mayores de 9 años. Se describen exhaustivamente los síntomas y signos observados por edad. Se hospitalizaron a 8 pacientes, uno con un síndrome inflamatorio multisistémico. No hubo fallecimientos. Conclusiones: La COVID-19 es una enfermedad leve con un gran número de casos asintomáticos, con pocas hospitalizaciones y fallecimientos. El lugar principal de transmisión es el domicilio y el cierre de colegios debería ser el último recurso para controlar la pandemia. No se pudo describir un cuadro clínico característico de la enfermedad. (AU)

Objectives: In Spain, the tools to diagnose COVID-19 were available in primary care from May 2020. Previously most studies described inpatients, and fever and cough were the most frequent symptoms. This study aims to define the clinical picture of the pediatric COVID-19 in the community. Methods: A descriptive and analytical observational study was performed including pediatric cases (0-14y) from 255 pediatricians, proportionally distributed to its population, from primary health centers in Spain, from 12th May 2020 to 30th April 2021. Diagnostics were made by PCR detection of viral RNA, rapid antigen detection test or positive IgG serology. Results: There were 10,021 positive children included, 48.4% women, mean age 8,04±4.17 years. Infection was detected due to contact tracing (70.9%), compatible symptoms (18.8%). Household was the main source of transmission (64.9%), followed by school setting (10%) or unknown (9.9%). We did not find any significant differences in the incidence between holidays and school terms. 43.2% of the children were asymptomatic. Most frequent symptoms are rhinorrhea in <2y, fever in 3-8y and headache in >9y. An exhaustive description of objective and subjective symptoms by age is made. 18 patients were hospitalized, one with multisystem inflammatory syndrome in children. There were no deaths. Conclusions: Pediatric COVID-19 is a mild disease, with a large number of asymptomatic cases, with very few hospital admissions and deaths. The main setting for transmission is the household, and school closures should be a last resource measure during the COVID-19 pandemic. A specific clinical picture of pediatric COVID-19 was not found. (AU)

Fiebre sin foco / Unfocused fever

La fiebre sin foco (FSF) es uno de los motivos de consulta más frecuentes en Pediatría, y generalmente se debe a procesos infecciosos banales que no van a requerir realización de pruebas complementarias ni tratamiento antibiótico. Es por ello que conocer la etiología, diferente según la edad del paciente y el estado de inmunización y medio donde nos encontremos, así como realizar una correcta anamnesis y exploración física, con apoyo de los algoritmos disponibles, es imperativo para identificar aquellos pacientes que estén en riesgo de padecer una infección bacteriana grave (IBG). En ellos, habrá que hacer una petición justificada de pruebas complementarias y tratar de acuerdo con la etiología más frecuente. En los pacientes con bajo riesgo de IBG, que serán la mayoría, es preciso tranquilizar a los cuidadores, explicando los signos y síntomas de alerta de progresión o gravedad, combatir la fiebrefobia, prescribiendo antitérmicos para tratar el malestar asociado, y reevaluar cuando sea preciso (AU)

Estudio multicéntrico nacional sobre la organización de las consultas de Pediatría de Atención Primaria en España durante la primera ola de la pandemia de COVID-19 / Nationwide multicentre study on the organization of primary care paediatrics services in the first wave of the COVID-19

Introducción: la pandemia de COVID-19 ha originado cambios organizativos en los centros de Atención Primaria (AP). El objetivo de este estudio es conocer los cambios producidos en las consultas de Pediatría de AP durante la primera ola de la pandemia por COVID-19. Material y métodos: estudio observacional, descriptivo, retrospectivo, multicéntrico y de ámbito nacional, a través de una encuesta dirigida a los pediatras de Atención Primaria (PAP) distribuida en junio de 2020. Se recogieron datos desde el 16 de marzo al 10 de mayo de 2020, dividido en cuatro periodos de dos semanas cada uno. Se preguntó sobre la forma de trabajar en los centros durante ese periodo: existencia de sistema de triaje, modalidad de atención, presencial o telefónica, y volumen de consultas atendidas. Resultados: se consideraron válidas 105 encuestas de las 110 contestadas por PAP. Participaron pediatras de 17 comunidades autónomas (el 72,4% de medio urbano). Cubrían una población de 107 715 pacientes. Realizaron consulta telemática el 90,5% (38,1% antes de la pandemia). En todos los centros se realizó triaje. La media de pacientes atendidos por profesional en cada uno de los periodos considerados fue de 144, 114, 123, 136 (277, 214, 207 y 233 en los mismos periodos del año 2019). En el 88,6% de cupos se realizaron visitas presenciales del programa de salud infantil (PSI). De toda la población atendida, los PAP notificaron ingresos por cualquier motivo de 79 pacientes y en la unidad de cuidados intensivos (UCI) de siete. No se les notificó ningún fallecimiento. Conclusiones: durante el periodo inicial de pandemia COVID-19 se registró en las consultas de Pediatría de AP un aumento muy importante de la consulta telemática y, paralelamente, una disminución significativa de la consulta presencial. Se instauraron sistemas de triaje. Se mantuvo una actividad muy alta en el PSI. Hubo un número muy bajo de ingresos y casos graves (AU)

Introduction: the COVID-19 pandemic has driven changes in the organization of care delivery in primary care (PC) centres. The objective of our study was to describe the changes in PC paediatric care that took place in the first wave of the COVID-19 pandemic. Material and methods: we conducted a nationwide, multicentre, retrospective, observational and descriptive study through a survey of PC paediatricians with distribution of the questionnaire in June 2020. We collected data from March 16 to May 10, 2020, divided in four 2-week periods. We asked about care delivery in these centres during this period: use of triage systems, modalities of care delivery (in person or by telephone) and volume of visits. Results: we received 105 responses by PC paediatricians, of which 110 were considered valid. We obtained responses from paediatricians in 17 autonomous communities (72.4% in urban settings). Respondents served a cumulative population of 107 715 patients. A total of 90.5% provided remote care (38.1% did before the pandemic). Triage was conducted in all centres. The mean number of patients managed per paediatrician in each of the time intervals under study was 144, 114, 123 and 136 (compared to 277, 214, 207 and 233 in the same periods in 2019). In 88.6% of the caseloads, in-person appointments were conducted as part of the child health programme (CHP). The total number of hospital admissions for any reason in the cumulative catchment population was of 79 patients, and the number of admissions to the intensive care unit was 7. The respondents did not report any deaths. Conclusions: in the first wave of the COVID-19 pandemic, there was a substantial increase in remote primary care paediatric visits parallel to a significant decrease in in-person visits. Triage systems were implemented. There was still substantial activity in the CHP. The number of hospital admissions and cases of serious disease was very low (AU)

Pyogenic sacroiliitis in children-a diagnostic challenge.

Osteoarticular infections in paediatric patients are associated with significant morbidity. Pyogenic sacroiliitis is rare and accounts for approximately 1-2% of osteoarticular infections in children. Diagnosis of this disease has been difficult in the past due to its deep location and may be delayed due to the lack of specific clinical signs and symptoms. We identified 11 paediatric patients with clinical-radiological signs of pyogenic sacroiliitis during an 8-year period and observed an unusual cluster of four cases during the last 11 months. Early diagnosis was possible due to a reproducible clinical pattern as well as radiological evidences of infection using magnetic resonance imaging and/or bone scintigraphy; most patients having predisposing factors. Staphylococcus aureus was the sole causative agent identified. All patients including two children with associated muscle abscesses were managed conservatively with antibiotic therapy only and showed good clinical response with no sequelae during follow-up. An algorithm for the correct and prompt diagnosis of this pathology is proposed. Standardised optimal therapy remains to be defined.

Epidemiología de la colonización nasofaríngea por Streptococcus pneumoniae en niños menores de 6 años de la ciudad de Sevilla / Epidemiology of nasopharyngeal carriage of Streptococcus pneumoniae in children < 6 years old in Seville

Introducción: El objetivo de la investigación fue estudiar la epidemiología de la colonización nasofaríngea por Streptococcus pneumoniae (S. pneumoniae) tras la introducción de la vacuna conjugada neumocócica heptavalente (VCN7).Métodos Se obtuvieron muestras NF en 848 niños > 6 meses y<6 años atendidos en cuatro centros de salud (niños sanos) y en dos urgencias hospitalarias (niños enfermos) de Sevilla durante el período comprendido entre el 1/2/2005 y el 31/6/2008. Resultados De forma global 278 (33%) niños estaban colonizados por S. pneumoniae, la asistencia a guardería o colegio (OR: 2,21; IC 95%: 1,54-3,15; p=0,0001) y la edad < 3 años (OR: 1,87; IC 95%: 1,3-2,69; p=0,001) fueron predictores independientes de la colonización neumocócica. La utilización reciente de antibióticos tuvo un efecto protector (OR: 0,68; IC 95%: 0,48-0,94; p=0,02). Cobertura vacunal VCN7 41%. Se encontró una menor frecuencia de colonización por serotipos vacunales (SV) en aquellos niños (..) (AU)

Introduction: The aim of this investigation was to study the epidemiology of nasopharyngeal (NP) colonization with Streptococcus pneumoniae after the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7).Methods: NP swabs were obtained from 848 children aged 6 months to six years seen in four primary care centres (healthy children) and in two emergency depeartments (sick children) from Seville. The study was conducted between February 2005 and June 2008.Results: A total of 278 (33%) children carried S. pneumoniae. Pneumococcal colonization was independently predicted by school attendance or child care participation (OR 2.21; 95% CI 1.54- 3.15; P=.0001)and younger age. Recent antibiotic use was protective (OR 0.68; 95% CI 0.48-0.94; P=.02). PCV7 uptake was 41%. Risk of carriage of PCV7- type pneumococci was lower among children who had (..) (AU)