ABSTRACT
Analytical treatment interruption (ATI) is widely acknowledged as an essential component of studies to advance our understanding of HIV cure, but discussion has largely been focused on adults. To address this gap, we reviewed evidence related to the safety and utility of ATI in paediatric populations. Three randomised ATI trials using CD4 T-cell and clinical criteria to guide restart of antiretroviral therapy (ART) have been conducted. These trials found low risks associated with ATI in children, including reassuring findings pertaining to neurocognitive outcomes. Similar to adults treated during acute infection, infants treated early in life have shifts in virological and immunological parameters that increase their likelihood of achieving ART-free viral control. Early ART limits the size and diversity of the viral reservoir and shapes effective innate and HIV-specific humoral and cellular responses. Several cases of durable ART-free viral control in early treated children have been reported. We recommend that, where appropriate for the study question and where adequate monitoring is available, ATI should be integrated into ART-free viral control research in children living with HIV. Paediatric participants have the greatest likelihood of benefiting and potentially the most years to prospectively realise those benefits. Excluding children from ATI trials limits the evidence base and delays access to interventions.
ABSTRACT
After sporadic reports of post-treatment control of HIV in children who initiated combination anti-retroviral therapy (cART) early, we prospectively studied 284 very-early-cART-treated children from KwaZulu-Natal, South Africa, after vertical HIV transmission to assess control of viremia. Eighty-four percent of the children achieved aviremia on cART, but aviremia persisting to 36 or more months was observed in only 32%. We observed that male infants have lower baseline plasma viral loads (P = 0.01). Unexpectedly, a subset (n = 5) of males maintained aviremia despite unscheduled complete discontinuation of cART lasting 3-10 months (n = 4) or intermittent cART adherence during 17-month loss to follow-up (n = 1). We further observed, in vertically transmitted viruses, a negative correlation between type I interferon (IFN-I) resistance and viral replication capacity (VRC) (P < 0.0001) that was markedly stronger for males than for females (r = -0.51 versus r = -0.07 for IFN-α). Although viruses transmitted to male fetuses were more IFN-I sensitive and of higher VRC than those transmitted to females in the full cohort (P < 0.0001 and P = 0.0003, respectively), the viruses transmitted to the five males maintaining cART-free aviremia had significantly lower replication capacity (P < 0.0001). These data suggest that viremic control can occur in some infants with in utero-acquired HIV infection after early cART initiation and may be associated with innate immune sex differences.
ABSTRACT
The EPICO (Spanish general registry of COVID-19 in children)-SEHOP (Spanish Society of Pediatric Hematology and Oncology) platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 14.7%), except in children with recent alloHSCT (less than 300 days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies.
Subject(s)
COVID-19 , Comorbidity , Hematopoietic Stem Cell Transplantation , Neoplasms , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/complications , Child , Male , Adolescent , Female , Child, Preschool , Risk Factors , Neoplasms/epidemiology , Neoplasms/therapy , Infant , Spain/epidemiology , Registries , Transplantation, HomologousABSTRACT
Introduction: Initiation of antiretroviral treatment (ART) in patients early after HIV-infection and long-term suppression leads to low or undetectable levels of HIV RNA and cell-associated (CA) HIV DNA and RNA. Both CA-DNA and CA-RNA, overestimate the size of the HIV reservoir but CA-RNA as well as p24/cell-free viral RNA can be indicators of residual viral replication. This study describes HIV RNA amounts and levels of cytokines/soluble markers in 40 well-suppressed adolescents who initiated ART early in life and investigated which viral markers may be informative as endpoints in cure clinical trials within this population. Methods: Forty adolescents perinatally infected with HIV on suppressive ART for >5 years were enrolled in the CARMA study. HIV DNA and total or unspliced CA-RNA in PBMCs were analyzed by qPCR/RT-qPCR and dPCR/RT-dPCR. Cell-free HIV was determined using an ultrasensitive viral load (US-VL) assay. Plasma markers and p24 were analyzed by digital ELISA and correlations between total and unspliced HIV RNA and clinical markers, including age at ART, Western Blot score, levels of cytokines/inflammation markers or HIV CA-DNA, were tested. Results: CA-RNA was detected in two thirds of the participants and was comparable in RT-qPCR and RT-dPCR. Adolescents with undetectable CA-RNA showed significantly lower HIV DNA compared to individuals with detectable CA-RNA. Undetectable unspliced CA-RNA was positively associated with age at ART initiation and Western Blot score. We found that a higher concentration of TNF-α was predictive of higher CA-DNA and CA-RNA. Other clinical characteristics like US-VL, time to suppression, or percent CD4+ T-lymphocytes were not predictive of the CA-RNA in this cross-sectional study. Conclusions: Low CA-DNA after long-term suppressive ART is associated with lower CA-RNA, in concordance with other reports. Patients with low CA-RNA levels in combination with low CA-DNA and low Western Blot scores should be further investigated to characterize candidates for treatment interruption trials. Unspliced CA-RNA warrants further investigation as a marker that can be prioritized in paediatric clinical trials where the sample volume can be a significant limitation.
Subject(s)
Cell-Free Nucleic Acids , HIV Infections , Humans , Adolescent , Child , Cross-Sectional Studies , RNA , Anti-Retroviral Agents/therapeutic use , Cytokines , HIV Infections/drug therapy , DNAABSTRACT
Desde que en marzo de 2020 se declarara la pandemia COVID-19 hemos aprendido muchas cosas del coronavirus SARS-CoV-2, y de su papel en la enfermedad pediátrica.Los niños se infectan en un porcentaje bastante similar a los adultos, si bien en la mayoría de las ocasiones sufren cuadros leves o asintomáticos. Alrededor de un 1% de infectados precisan hospitalización, menos de un 0,02% precisan cuidados intensivos, y la mortalidad es muy baja y generalmente en niños con comorbilidades. Los cuadros clínicos más habituales son infecciones respiratorias de vías altas o bajas, cuadros gastrointestinales y con mayor gravedad el síndrome inflamatorio multisistémico (MIS-C). La mayoría de los episodios no precisan tratamiento, salvo el MIS-C. El remdesivir se ha empleado generalmente como tratamiento compasivo y aún está por definir su papel.El recién nacido puede infectarse, si bien la transmisión vertical es muy baja (<1%), y se ha demostrado que el bebé puede cohabitar de manera segura con su madre y recibir lactancia materna. En general las infecciones neonatales han sido leves.La atención primaria ha soportado una parte muy importante del manejo de la pandemia en pediatría. Se han producido numerosos daños colaterales derivados de la dificultad de acceso a la asistencia y del aislamiento que han sufrido los niños. La salud mental de la población pediátrica se ha visto seriamente afectada. A pesar de que se ha demostrado que la escolarización no ha supuesto un incremento de los contagios, sino más bien todo lo contrario. Es fundamental seguir manteniendo las medidas de seguridad que permitan hacer de las escuelas un lugar seguro, tan necesario no solo para la educación infantil, sino para su salud en general. (AU)
Since the COVID-19 pandemic was declared in March 2020, we have learned a lot about the SARS-CoV-2 coronavirus, and its role in pediatric pathology.Children are infected in a rate quite similar to adults, although in most cases they suffer mild or asymptomatic symptoms. Around 1% of those infected require hospitalization, less than 0.02% require intensive care, and mortality is very low and generally in children with comorbidities. The most common clinical diagnoses are upper or lower respiratory infections, gastrointestinal infection and, more seriously, multisystemic inflammatory syndrome (MIS-C). Most episodes do not require treatment, except for MIS-C. Remdesivir has been widely used as a compassionate treatment and its role has yet to be defined.The newborn can become infected, although vertical transmission is very low (<1%) and it has been shown that the baby can safely cohabit with its mother and be breastfed. In general, neonatal infections have been mild.Primary care has supported a very important part of the management of the pandemic in pediatrics. There has been numerous collateral damage derived from the difficulty of access to care and the isolation suffered by children. The mental health of the pediatric population has been seriously affected. Although it has been shown that schooling has not led to an increase in infections, but rather the opposite. It is essential to continue maintaining the security measures that make schools a safe place, so necessary not only for children's education, but for their health in general. (AU)
Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Child , Pandemics , Coronavirus Infections/epidemiology , Severe acute respiratory syndrome-related coronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/diagnosis , Spain , Primary Health Care , SchoolsABSTRACT
Se ha descrito un nuevo síndrome inflamatorio multisistémico pediátrico vinculado a SARS-CoV-2. Este cuadro presenta una expresividad clínica variable y se asocia a infección activa o reciente por SARS-CoV-2. En este documento se revisa la literatura existente por parte de un grupo multidisciplinar de especialistas pediátricos. Posteriormente, se realizan recomendaciones sobre estabilización, diagnóstico y tratamiento de este síndrome
A new paediatric multisystem inflammatory syndrome, linked to SARS-CoV-2, has been described. The clinical picture is variable and is associated with an active or recent infection due to SARS-CoV-2. A review of the existing literature by a multidisciplinary group of paediatric specialists is presented in this document. Later, they make recommendations on the stabilisation, diagnosis, and treatment of this síndrome
Subject(s)
Humans , Child , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Systemic Inflammatory Response Syndrome/complications , Consensus , Diagnosis, Differential , Systemic Inflammatory Response Syndrome/prevention & control , Hospitalization , BetacoronavirusABSTRACT
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Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Coronavirus Infections/drug therapy , Coronavirus Infections/diagnosis , Severity of Illness Index , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Spain/epidemiologyABSTRACT
No disponible
Subject(s)
Humans , Infant, Newborn , Child , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Pandemics , Spain/epidemiologyABSTRACT
Introducción: La gripe es una enfermedad generalmente benigna, pero en ocasiones puede ocasionar complicaciones graves. Existe controversia sobre los beneficios del tratamiento con antivirales. Objetivos: Proporcionar unas recomendaciones sobre el tratamiento con oseltamivir en pacientes pediátricos con gripe, basadas en los mejores datos disponibles y válidas en nuestro medio. Métodos: El Grupo de Infecciones Respiratorias de la Sociedad Española de Infectología Pediátrica llevó a cabo una revisión de la bibliografía. Los hallazgos se analizaron mediante la metodología GRADE, y se elaboraron unas recomendaciones. Resultados: No se recomienda el uso sistemático de pruebas diagnósticas para la gripe en el ámbito ambulatorio y en urgencias hospitalarias en pacientes inmunocompetentes con un cuadro clínico compatible. No se recomienda el uso de antivirales a la gran mayoría de los pacientes sanos y asmáticos con gripe o sospecha de gripe estacional, si el objetivo es prevenir eventos graves. No se recomienda el uso de oseltamivir de forma sistemática en pacientes hospitalizados con gripe. Se recomienda tratar con oseltamivir a los pacientes con gripe y neumonía o enfermedad grave o a los pacientes críticos, especialmente durante las primeras 48 h de enfermedad. Se recomienda el tratamiento de los pacientes con factores de riesgo, teniendo en cuenta su enfermedad de base. La vacunación antigripal, junto a las medidas básicas de evitación, continúan siendo la principal herramienta en la prevención de la gripe. Conclusión: En algunas situaciones hay datos suficientes para emitir recomendaciones claras. En otras situaciones los datos son incompletos y solo permiten hacer recomendaciones débiles
Introduction: Influenza is a generally a benign disease, but occasionally it can cause serious complications. There is controversy about the benefits of antiviral treatment. Objectives: To provide some recommendations on the treatment with oseltamivir in paediatric patients with influenza, based on the best data available and valid in our environment. Methods: The Respiratory Infections Group of the Spanish Society of Paediatric Infectious Diseases carried out a review of the literature. The findings were analysed using the GRADE methodology, and recommendations were made. Results: The systematic use of diagnostic tests for influenza in the outpatient setting, or in the emergency room, in immunocompetent patients with a compatible clinical picture is not recommended. If the aim is to prevent serious events, the use of antivirals is not recommended for the vast majority of healthy and asthmatic patients with influenza or suspected seasonal flu. The systematic use of oseltamivir in patients admitted to hospital with influenza is not recommended. Oseltamivir treatment is recommended in any patients with influenza and pneumonia or severe illness, and critically ill patients, especially during the first 48 hours of illness. The treatment of patients with risk factors is recommended, considering their underlying disease. Influenza vaccination, together with basic isolation measures, continue to be the main tool in the prevention of influenza. Conclusion: In some situations, there are sufficient data to issue clear recommendations. In other situations, the data are incomplete, and only allows weak recommendations
Subject(s)
Humans , Child , Adolescent , Antiviral Agents/administration & dosage , Influenza, Human/drug therapy , Oseltamivir/administration & dosage , Age Factors , Antiviral Agents/adverse effects , Critical Illness , Influenza, Human/complications , Influenza, Human/diagnosis , Oseltamivir/adverse effects , Risk Factors , Time FactorsABSTRACT
Objetivos Se describe un brote de tuberculosis que tuvo lugar en un centro escolar a partir de un caso secundario. Métodos Estudio de contactos. Evaluación clínica de los pacientes expuestos. Radiografía, toma de muestras (jugo gástrico) y seguimiento clínico de todos los niños con Mantoux positivo. Diagnóstico diferencial entre enfermedad tuberculosa (TB) e infección tuberculosa latente (ITL).Resultados Se identificaron un grupo de alta exposición al caso índice (> 6 horas al día durante 3 meses, 17 niños) y un grupo de exposición esporádica (< 6 horas al día, 82 niños). Seis de 17 niños (35%) del grupo de alta exposición cumplieron criterios clínicos o microbiológicos de TB. Cuatro cumplieron criterios clínicos, con cultivo de jugo gástrico negativo. Los otros dos, asintomáticos y con radiografía normal, tuvieron un cultivo positivo para Mycobacterium tuberculosis (M. tuberculosis). La tasa de contagio (TB+ITL) en este grupo fue del 94%. Un niño (1,2%) entre 82 de los expuestos de forma esporádica al caso índice tuvo criterios de TB. Entre el personal del colegio, la tasa de ITL fue del 15%. No hubo ningún enfermo de tuberculosis entre el personal, al margen del caso índice. El riesgo relativo de padecer tuberculosis entre los niños más expuestos fue de 28,5 (IC 95%: 3-250).Conclusiones La exposición continuada a un enfermo bacilífero puede generar casi un 100% de infecciones en grupos escolares cerrados, y una considerable tasa de ataque. En este escenario, podría estar indicada la toma de jugo gástrico a todos los pacientes con Mantoux positivo, para identificar precozmente TB subclínicas y para tener más probabilidades de aislar el M. tuberculosis. El beneficio potencial de esta identificación puede alcanzar a toda la cohorte (AU)
Aims To describe a tuberculosis outbreak in a primary school arising from a secondary case. Methods Contact study and clinical study of exposed patients. Chest x-ray, gastric aspirate processing, and clinical evaluation of all children with a positive tuberculin skin test (TST) were recorded. Differential diagnosis between tuberculosis disease (TB) and latent tuberculosis infection (LTI).Results Two groups were identified: one of higher exposure to the index case (>6hours/day, for 3 months; n=17 children) and one of sporadic exposure (<6hours/day; n=82 children). Clinical or bacteriological criteria for diagnosing TB were seen in 6 out of 17 (35%) highly exposed children. Four of them had clinical or radiological criteria. The other two children were asymptomatic and had a normal chest X ray, but had a positive gastric aspirate for M. tuberculosis. The overall infection rate (TB+LTI) was 94%. One child out of 82 (1.2%) sporadically exposed children had radiological criteria for TB. Staff infection rate was 15%. Apart from the index case, there were no other tuberculosis cases among the staff. Relative risk (RR) of exposed children was 28.5 (95% CI: 3-250).Conclusions Prolonged exposure to a baciliferous patient may infect almost every child exposed in closed groups. It can also cause a high attack rate. In this scenario, routine gastric aspirate may be considered for all children with a positive TST. It may identify early subclinical TB with an increased probability of isolating the M. tuberculosis. The potential benefit of this isolation may reach the entire cohort (AU)