Comparison of Epidemiologic and Clinical COVID-19 Profiles in Children in Argentina, During Circulation of Original and Variant (Alpha, Gamma and Lambda) Strains.

BACKGROUND: Information on the impact of the different variants in children in Latin America is scarce. The objective of this study was to describe epidemiologic and clinical features of COVID-19 infection in children under 18 years of age in Argentina, comparing the periods before and after the circulation of new variants. METHODS: Observational, cross-sectional, multicentric, analytical study. All patients under 18 years of age with confirmed SARS-CoV-2 infection admitted at 22 healthcare centers were included. Two study periods were established: Period 1 (EW10-2020 to EW12-2021) for the Wuhan strain; Period 2 (EW13 to EW35 2021) for Alpha, Gamma, Delta and Lambda variants. FINDINGS: A total of 6330 confirmed cases were included. Period 1: 3575 (56.5%), period 2: 2755 (43.5%). During period 2, a lower number of asymptomatic cases was observed, while general, respiratory and neurologic signs and symptoms increased in all age groups. Oxygen therapy requirement was higher during the first period (36.7% vs 19.1%; P < 0.001). No significant differences were observed in the rates of severe or critical cases (6.3% vs 5,4%; P = 0.102), intensive care admission (2.1% vs 2%; P < 0.656) or case fatality (0.3% vs 0.5 %; P < 0.229). MIS-C cases occurred more frequently during the first period (1.9% vs 1.1%; P = 0.009). INTERPRETATION: The clinical spectrum of COVID-19 in Argentina has evolved. With the emergence of new variants, although the number of asymptomatic cases declined, numbers of severe and critical cases, as well as case fatality rates in children, remained unchanged.

Rhizoma Gastrodiae Water Extract Modulates the Gut Microbiota and Pathological Changes of P-TauThr231 to Protect Against Cognitive Impairment in Mice.

Gastrodiae Rhizoma and its active constituents are known to exhibit neuroprotective effects in Alzheimer's disease (AD). However, the effect of Rhizoma Gastrodiae water extract (WERG) on AD and the detailed mechanism of action remain unclear. In this study, the mechanism of action of WERG was investigated by the microbiome-gut-brain axis using a D-galactose (D-gal)/AlCl3-induced AD mouse model. WERG improved the cognitive impairment of D-gal/AlCl3-induced mice. The expression level of p-Tauthr231 in the WERG-H treatment group was decreased, and p-Tauthr231 was found negative in hippocampal DG, CA1, and CA3 regions. Here, the diversity and composition of the gut microbiota were analyzed by 16sRNA sequencing. WERG-H treatment had a positive correlation with Firmicutes, Bacilli, Lactobacillus johnsonii, Lactobacillus murinus, and Lactobacillus reuteri. Interestingly, the Rikenellaceae-RC9 gut group in the gut increased in D-gal/AlCl3-induced mice, but the increased L. johnsonii, L. murinus, and L. reuteri reversed this process. This may be a potential mechanistic link between gut microbiota dysbiosis and P-TauThr231 levels in AD progression. In conclusion, this study demonstrated that WERG improved the cognitive impairment of the AD mouse model by enriching gut probiotics and reducing P-TauThr231 levels.

Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex.

Mitochondrial ATP synthase is vital not only for cellular energy production but also for energy dissipation and cell death. ATP synthase c-ring was suggested to house the leak channel of mitochondrial permeability transition (mPT), which activates during excitotoxic ischemic insult. In this present study, we purified human c-ring from both eukaryotic and prokaryotic hosts to biophysically characterize its channel activity. We show that purified c-ring forms a large multi-conductance, voltage-gated ion channel that is inhibited by the addition of ATP synthase F1 subcomplex. In contrast, dissociation of F1 from FO occurs during excitotoxic neuronal death suggesting that the F1 constitutes the gate of the channel. mPT is known to dissipate the osmotic gradient across the inner membrane during cell death. We show that ATP synthase c-subunit knock down (KD) prevents the osmotic change in response to high calcium and eliminates large conductance, Ca2+ and CsA sensitive channel activity of mPT. These findings elucidate the gating mechanism of the ATP synthase c-subunit leak channel (ACLC) and suggest how ACLC opening is regulated by cell stress in a CypD-dependent manner.

Oropharyngeal meningococcal carriage in children and adolescents, a single center study in Buenos Aires, Argentina.

BACKGROUND: Neisseria meningitidis (Nm) pharyngeal carriage is a necessary condition for invasive disease. We present the first carriage study in children in Buenos Aires, Argentina, considering 2017 as a transition year. Aims: to assess the rate of Nm carriage, to determine genogroup, clonal complex and outer membrane protein distribution, to determine carriage risk factors by age. METHODS: Cross-sectional study including children 1-17 yrs, at Ricardo Gutiérrez Children's Hospital in Buenos Aires 2017. Oro-pharyngeal swabs were taken and cultured within a short time after collection. Genogroup was determined by PCR and clonal complex by MLST. Categorical variables were analyzed. RESULTS: A total of 1,751 children were included. Group 1: 943 children 1-9 yrs, 38 Nm were isolated; overall carriage 4.0%. Genogroup distribution: B 26.3%, W 5.3%, Y 2.6%, Z 5.3%, other groups 7.9% and capsule null (cnl) 52.6%. Participating in extracurricular activities was the only independent predictor of Nm carriage. Group 2: 808 children 10-17 yrs, 76 Nm were isolated; overall carriage 9.4%. Genogroup distribution: B 19.7%, C 5.3%, W 7.9%, Y 9.2%, Z 5.3%, other groups 7.9% and cnl 44.7%. Independent predictors of carriage: attending pubs/night clubs and passive smoking (adjusted OR: 0.55, 95%CI = 0.32-0.93; p = 0.025). CONCLUSIONS: Overall carriage was higher in 10-17 yrs. The isolates presenting the cnl locus were prevalent in both age groups and genogroup B was the second most frequent.

Bioleaching of realgar nanoparticles using the extremophilic bacterium Acidithiobacillus ferrooxidans DLC-5

BACKGROUND: This paper presents micro- and nano-fabrication techniques for leachable realgar using the extremophilic bacterium Acidithiobacillus ferrooxidans (A. ferrooxidans) DLC-5. RESULTS: Realgar nanoparticles of size ranging from 120 nm to 200 nm were successfully prepared using the highenergy ball mill instrument. A. ferrooxidans DLC-5 was then used to bioleach the particles. The arsenic concentration in the bioleaching system was found to be increased significantly when compared with that in the sterile control. Furthermore, in the comparison with the bioleaching of raw realgar, nanoparticles could achieve the same effect with only one fifth of the consumption. CONCLUSION: Emphasis was placed on improving the dissolvability of arsenic because of the great potential of leachable realgar drug delivery in both laboratory and industrial settings

Recomendaciones ante exposición a varicela en el ámbito hospitalario / Recommendations concerning exposure to chickenpox in hospital settings

La varicela es una infección viral aguda, con elevada transmisibilidad. Si bien en la mayor parte de los casos cursa como una infección benigna, puede presentar complicaciones en ciertos grupos de riesgo fundamentalmente en el ámbito hospitalario. El siguiente artículo resume los aspectos más importantes del abordaje de los pacientes expuestos a varicela, focalizando en el manejo epidemiológico de los contactos susceptibles en el ámbito de los servicios de salud

Chickenpox is an acute viral infection, with high transmissibility. Although, in most cases, it is a benign infection, it can cause complications in certain risk groups, mainly in the hospital setting. The following article summarizes the most important aspects of the management of patients exposed to varicella, focusing on the epidemiological management of susceptible contacts in the field of health care services

Fenilcetonuria de diagnóstico tardío y mutaciones asociadas en una familia ecuatoriana / Phenylketonuria of late diagnosis and associated mutations in an Ecuadorian family

La fenilcetonuria es un error innato del metabolismo, producido por mutaciones en el gen de la fenilalanina hidroxilasa. Se describe el caso de un adolescente de 15 años con diagnóstico tardío de fenilcetonuria, quien presenta retardo mental severo, convulsiones e hipopigmentación. En este estudio se realizó el diagnóstico molecular de fenilcetonuria y se detectó la mutación p.R252W en homocigosis en el gen que codifica para la fenilalanina hidroxilasa. La presencia de esta variante nos permitió inferir la falta de respuesta a la terapia con sapropterina, medicamento que actúa como cofactor de la enzima, por la ausencia de actividad enzimática residual reportada para esta variante. Debido al retraso psicomotor del paciente, se decidió aplicar terapia lúdica y fortalecimiento muscular a través de la intervención fisioterapéutica; sin embargo, no se observó una mejoría permanente al aplicar este tratamiento, motivado por la falta de continuidad.

Phenylketonuria is an inborn error of metabolism due to mutations on the phenylalanine hydroxylase gene. We described the case of a 15 years old-adolescent with late diagnosis of phenylketonuria, who presents severe mental retardation, convulsions and hypopigmentation. In this study, the molecular diagnosis of phenylketonuria was performed, detecting p.R252W mutation in homozygous state on the phenylalanine hydroxylase gene. The presence of this variant allowed us to infer the lack of response to drug therapy with sapropterina which works as an enzyme cofactor, due to the absence of residual enzymatic activity reported for the p.R252W variant. Physical therapy was applied through playful therapy and muscular strengthening, because of the psychomotor retardation present in the patient. The failing in continuing with the physical therapy program stopped the patient´s improvement.

Meningitis por Haemophilus influenzae b: ¿estamos ante una reemergencia? 24 años de experiencia en un hospital pediátrico / Haemophilus influenzae type B meningitis: Is there a re-emergence? 24 years of experience in a children's hospital

Introducción. Haemophilus influenzae b era la principal causa de meningitis bacteriana en menores de 5 años. Después de la introducción de la vacuna al calendario (1998), se observó un descenso significativo de la incidencia, pero, en los últimos años, hubo un aumento. Los objetivos de este estudio fueron describir las características y analizar la curva epidémica de los casos de meningitis por Haemophilus influenzae b (MHib) comparando los períodos pre- y posvacunación. Material y métodos. Estudio de series temporales. Se incluyeron todos los pacientes internados por MHib en el Hospital de Niños "R. Gutiérrez" (enero de 1992-mayo de 2016). Se compararon las tasas de hospitalización antes (prevacunación) y después (posvacunación) de la introducción de la vacuna. Se dividió la etapa posvacunación en tres períodos similares. Resultados. Fueron admitidos 85 pacientes con MHib (73,3% prevacunación). Las características clínicas y sociodemográficas de los casos en ambos períodos no mostraron diferencias. Prevacunación: 10,5 casos/año; y posvacunación: 0,7 casos/año. A partir de 2014, se observó un aumento. Tasa de letalidad: 4,8% (todos prevacunación). Datos posvacunación (n= 15): 40% del esquema primario completo, 40% del esquema atrasado para la edad. Reducción global de la tasa hospitalaria de MHib de 89,8% (IC 95%: -82,79-93,96%; p < 0,001) en el período posvacunación. Al analizar los diferentes períodos posvacunación, se observa una caída en la reducción a lo largo del tiempo. Conclusiones. Se observó una disminución muy importante de las hospitalizaciones por MHib pos introducción de la vacuna, pero, en los últimos años, se evidenció un aumento de estos casos sin modificaciones en las características de los pacientes.

Introduction. Haemophilus influenzae type B (Hib) used to be the main cause of bacterial meningitis in children younger than 5 years old. Following the introduction of the Hib vaccine in the immunization schedule (1998), its incidence reduced significantly but it has increased over the last years. The objectives of this study included describing the characteristics and analyzing the epidemic curve of Haemophilus influenzae type B (Hib) meningitis by comparing the pre- and postimmunization periods. Material and methods. Time-series study. All patients hospitalized with Hib meningitis at Hospital de Niños "R. Gutiérrez" (January 1992-May 2016). Hospitalization rates were compared before (pre-immunization) and after (post-immunization) the introduction of the Hib vaccine. The post-immunization period was divided into three similar periods. Results. Eighty-five patients with Hib meningitis were admitted (73.3% in the pre-immunization period). No differences were observed in relation to the clinical and sociodemographic characteristics of cases in both periods. Pre-immunization: 10.5 cases/year; postimmunization: 0.7 cases/year. As of 2014, the rate has increased. Lethality rate: 4.8% (all preimmunization). Post-immunization data (n= 15): 40% had completed their primary immunization schedule, 40% were delayed on the immunization schedule for their age. Overall reduction in the hospital rate of Hib meningitis by 89.8% (95% confidence interval: -82.79-93.96%, p < 0.001) in the post-immunization period. The analysis of the different post-immunization periods shows a decline in reduction over time. Conclusions. A very significant reduction in hospitalizations due to Hib meningitis was observed after the Hib vaccine was introduced; however, over the past years, the number of cases has increased although no changes have been observed in patient characteristics.

Haemophilus influenzae type B meningitis: Is there a re-emergence? 24 years of experience in a children's hospital. / Meningitis por Haemophilus influenzae b: ¿estamos ante una reemergencia? 24 años de experiencia en un hospital pediátrico.

INTRODUCTION: Haemophilus influenzae type B (Hib) used to be the main cause of bacterial meningitis in children younger than 5 years old. Following the introduction of the Hib vaccine in the immunization schedule (1998), its incidence reduced significantly but it has increased over the last years. The objectives of this study included describing the characteristics and analyzing the epidemic curve of Haemophilus influenzae type B (Hib) meningitis by comparing the pre- and postimmunization periods. MATERIALS AND METHODS: Time-series study. All patients hospitalized with Hib meningitis at Hospital de Niños "R. Gutiérrez" (January 1992-May 2016). Hospitalization rates were compared before (pre-immunization) and after (post-immunization) the introduction of the Hib vaccine. The post-immunization period was divided into three similar periods. RESULTS: Eighty-five patients with Hib meningitis were admitted (73.3% in the pre-immunization period). No differences were observed in relation to the clinical and sociodemographic characteristics of cases in both periods. Pre-immunization: 10.5 cases/year; postimmunization: 0.7 cases/year. As of 2014, the rate has increased. Lethality rate: 4.8% (all preimmunization). Post-immunization data (n= 15): 40% had completed their primary immunization schedule, 40% were delayed on the immunization schedule for their age. Overall reduction in the hospital rate of Hib meningitis by 89.8% (95% confidence interval: -82.79-93.96%, p < 0.001) in the post-immunization period. The analysis of the different post-immunization periods shows a decline in reduction over time. CONCLUSIONS: A very significant reduction in hospitalizations due to Hib meningitis was observed after the Hib vaccine was introduced; however, over the past years, the number of cases has increased although no changes have been observed in patient characteristics.

INTRODUCCIÓN: Haemophilus influenzae b era la principal causa de meningitis bacteriana en menores de 5 años. Después de la introducción de la vacuna al calendario (1998), se observó un descenso significativo de la incidencia, pero, en los últimos años, hubo un aumento. Los objetivos de este estudio fueron describir las características y analizar la curva epidémica de los casos de meningitis por Haemophilus influenzae b (MHib) comparando los períodos pre- y posvacunación. MATERIAL Y MÉTODOS: Estudio de series temporales. Se incluyeron todos los pacientes internados por MHib en el Hospital de Niños "R. Gutiérrez" (enero de 1992-mayo de 2016). Se compararon las tasas de hospitalización antes (prevacunación) y después (posvacunación) de la introducción de la vacuna. Se dividió la etapa posvacunación en tres períodos similares. RESULTADOS: Fueron admitidos 85 pacientes con MHib (73,3% prevacunación). Las características clínicas y sociodemográficas de los casos en ambos períodos no mostraron diferencias. Prevacunación: 10,5 casos/año; y posvacunación: 0,7 casos/año. A partir de 2014, se observó un aumento. Tasa de letalidad: 4,8% (todos prevacunación). Datos posvacunación (n= 15): 40% del esquema primario completo, 40% del esquema atrasado para la edad. Reducción global de la tasa hospitalaria de MHib de 89,8% (IC 95%: -82,79-93,96%; p < 0,001) en el período posvacunación. Al analizar los diferentes períodos posvacunación, se observa una caída en la reducción a lo largo del tiempo. CONCLUSIONES: Se observó una disminución muy importante de las hospitalizaciones por MHib pos introducción de la vacuna, pero, en los últimos años, se evidenció un aumento de estos casos sin modificaciones en las características de los pacientes.

[Community-acquired methicillin-resistant Staphylococcus aureus infections in children: multicenter trial]. / Estudio multicéntrico sobre las infecciones pediátricas por Staphylococcus aureus meticilino-resistente provenientes de la comunidad en la Argentina.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) isolates are increasingly frequent causes of skin and soft-tissue infections or invasive infections in many communities. Local data are scarce. OBJECTIVE: To determine the frequency, clinical features and outcome of infections caused by MRSA. MATERIAL AND METHODS: Prospective and multicentric study of surveillance for community-acquired S. aureus infections in children from Argentina. Infections meeting the definition of community-acquired were identified. Demographic and clinical data were collected. Antibiotic susceptibilities were determined in the clinical microbiology laboratory with the methodology of the NCCLS. RESULTS: From November 2006 to November 2007, 840 S. aureus infections were diagnosed, 447 of them were community-acquired. One hundred and thirty-five children with underlying disease or previous hospital admission were excluded. Two hundred and eighty one (62%) infections were community-acquired MRSA (CA-MRSA). The median age of children was 36 months (r:1-201), 60% were male. Among the CA-MRSA isolates, 62% were obtained from children with skin and soft-tissue infections, and 38% from children with invasive infections. Of them, osteomyelitis, arthritis, empyema and pneumonia were prevalent. Eigthteen percent of children had bacteremia and 11% sepsis. The rate of clindamycin resistance of CA-MRSA isolates was 10% and 1% for trimethoprim-sulfamethoxazole. Only 31% of children had appropriate treatment at admission. The median time of treatment delayed was 72 h. The median time of parenteral treatment was 6 days (r:1-70). In 72% of patients surgical treatment was required. Three children died (1%). CONCLUSIONS: CA-MRSA isolates account for a high percentage and number of infections in children of Argentina. Community surveillance of CA-MRSA infections is critical to determine the appropriate empiric antibiotic treatment for either local or invasive infections. Clindamycin resistance was under 15% in the strains tested. Clindamycin should be use when CA-MRSA infection is suspected in children.

Estudio multicéntrico sobre las infecciones pediátricas por Staphylococcus aureus meticilino resistente provenientes de la comunidad en la Argentina / Community acquired methicillin resistant Staphylococcus aureus infections in children: multicenter trial

En los últimos años se ha informacion diversas partes del mundo la aparición deinfecciones extrahospitalarias causadas por S.aureus resistentes a la meticilina (SAMRC). Losdatos de nuestro país son muy escasos y de informesindividuales.Objetivo. Determinar la frecuencia, las característicasclínicas y la evolución final de las infeccionescausadas por SAMRC.Material y métodos. Estudio prospectivo y multicéntricode vigilancia de las infecciones extrahospitalariaspor S. aureus en niños de la Argentina. Seincluyeron niños con alguna infección clínica y microbiológicamentedocumentada por S. aureus. Lasensibilidad a los antibióticos de las cepas aisladasse investigó según normas NCCLS.Resultados. Entre 11/2006 y 11/2007 se diagnosticaron840 infecciones por S. aureus. De ellas, 582(69 por ciento) fueron comunitarias. Se excluyeron 135 niñoscon enfermedad de base o internación previa enhospitales. Para el análisis se incluyeron 447 infecciones,de las cuales 281 (62 por ciento) fueron causadas porSAMRC. La mediana de edad fue de 36 meses (r: 1-201). Un 60 por ciento fueron varones. Prevalecieron lasinfecciones de piel y partes blandas (62 por ciento). Las infeccionesosteoarticulares, el empiema pleural y laneumonía fueron las formas invasivas más frecuentes.El 18 por ciento presentó bacteriemia y el 11 por ciento sepsis. El10 por ciento de las cepas fue resistente a clindamicina y el1 por ciento a trimetoprima-sulfametoxazol. Sólo el 31 por ciento tuvoun tratamiento concordante al ingreso. La medianade retraso en el tratamiento adecuado fue de 72 h. Lamediana del tratamiento parenteral fue de 6 días (r:1-70). El 72 por ciento requirió tratamiento quirúrgico, principalmentedrenaje de colecciones purulentas (87 por ciento).Fallecieron 3 niños (1 por ciento).Conclusiones. La tasa de infecciones causadas porSAMRC es alta en niños de nuestro país. Esto constituyeun alerta epidemiológico, particularmentepara los pediatras.

Molecular and epidemiologic analysis of enterovirus B neurological infection in Argentine children.

BACKGROUND: Human enteroviruses are one of the major causes of central nervous system (CNS) infections in pediatrics. STUDY DESIGN: We have studied 1242 children under 15 years old with suspicion of CNS infection from January 1998 to December 2003. CSF was obtained and molecular typing of human enterovirus B serotypes was performed by RT-PCR and sequencing of the N-terminal part of VP1 gene. RESULTS: According to the clinical syndromes, patients were grouped as aseptic meningitis (n=654, 52.6%), encephalitis (n=239, 19.2%), febrile seizures (n=153, 12.3%), febrile infant (n=84, 6.7%), neonatal disease (n=70, 5.6%),), acute flaccid paralysis (n=31, 2.4%) and acute disseminated encephalomyelitis (n=11, 0.9%). HEV was detected in 335/1242 CSF samples (26.97%) and was associated to aseptic meningitis (n=243, 72.5%); febrile infant (n=31, 9.2%); neonatal infection (n=26, 7.7%); encephalitis (n=25, 7.5%), febrile seizures (n=9, 2.68%); acute flaccid paralysis (n=1, 0.3%). Seasonal incidence of HEV-B species was analyzed showing that in Buenos Aires infections occur mainly during late spring and summer. Molecular serotyping was completed in 60/335 samples. Echovirus 30, Echovirus 9, Coxsackie B3 to B5 and Echovirus 33 were the most frequently identified. CONCLUSIONS: We showed that HEV are responsible for a considerable proportion of hospitalizations in children with central nervous system compromise reaching 27% of overall etiology.

Terapia de bloqueo: una nueva modalidad para el tratamiento de infecciones relacionadas con catéteres implantables / Antibiotic-lock therapy: a new approach for the treatment of implantable catheter-related infections

La infección relacionada con catéter es una de lasprincipales complicaciones en los pacientes concatéteres venosos centrales. El tratamiento convencionalimplica, muchas veces, retirar el dispositivo ytratamiento antibiótico prolongado. La terapiaantibiótica de bloqueo requiere la instilación de altasconcentraciones de antibióticos en la luz del catéter.Presentamos un paciente de nueve años con osteosarcomae infección asociada a catéter con reservorioimplantable por Pantoea agglomerans, tratadoexitosamente con terapia de bloqueo en el Hospitalde Niños “Dr. Ricardo Gutiérrez”. El objetivo fuecomunicar al pediatra la posibilidad de terapéuticaadicional (terapia de bloqueo) en niños con infecciónrelacionada con catéter.Palabras clave: infección relacionada con catéter, tratamiento,niños.

Terapia de bloqueo: una nueva modalidad para el tratamiento de infecciones relacionadas con catéteres implantables / Antibiotic-lock therapy: a new approach for the treatment of implantable catheter-related infections

La infección relacionada con catéter es una de lasprincipales complicaciones en los pacientes concatéteres venosos centrales. El tratamiento convencionalimplica, muchas veces, retirar el dispositivo ytratamiento antibiótico prolongado. La terapiaantibiótica de bloqueo requiere la instilación de altasconcentraciones de antibióticos en la luz del catéter.Presentamos un paciente de nueve años con osteosarcomae infección asociada a catéter con reservorioimplantable por Pantoea agglomerans, tratadoexitosamente con terapia de bloqueo en el Hospitalde Niños ¶Dr. Ricardo Gutiérrez÷. El objetivo fuecomunicar al pediatra la posibilidad de terapéuticaadicional (terapia de bloqueo) en niños con infecciónrelacionada con catéter.Palabras clave: infección relacionada con catéter, tratamiento,niños.(AU)