Diagnosis and treatment of 26 cases of adenovirus infection after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To analyze the clinical characteristics and prognosis of adenovirus infection after allogeneic hematopoietic stem cell transplantation. Methods: A total of 26 patients with adenovirus infection admitted to the posttransplant ward of the First Affiliated Hospital of Soochow University from 2018 to 2022 were enrolled. Their data on baseline and clinical characteristics, treatment, and follow-up were analyzed. Results: The median patient age was 30 (22, 44) years. Twenty-two patients received related haploid stem cell transplantation, three received unrelated stem cell transplantation, and one received umbilical cord stem cell transplantation. Antithymocyte globulin was included in the conditioning regimen in 25 patients. The median time of adenovirus infection was +95 (+44, +152) days. The median peripheral blood lymphocyte count was 0.30 (0.11, 0.69) × 10(9)/L. Twelve patients had acute graft-versus-host disease. Twenty-four patients received antirejection therapies at diagnosis. Sixteen cases had combined infection with other pathogens with adenovirus infection. Eight cases were diagnosed as asymptomatic infection, and 18 were diagnosed as adenovirus disease, including pneumonia (38.89% ) , gastrointestinal disease (38.89% ) , encephalitis (33.33% ) , hepatitis (5.56% ) , and urinary tract inflammation (5.56% ) . The age of >30 years was a risk factor for adenovirus disease (P=0.03) . Eighteen patients received tapering of immunosuppression, and all 26 patients received at least one antiviral drug. Other treatments included high-dose gamma globulin and donor lymphocyte infusion. Adenovirus infection improved in 10 cases and progressed in 16 cases. The median follow-up time was 30 (7, 237) days. Twenty-two patients died. The all-cause mortality rate was (88.5±7.1) % , and the attributable mortality rate was 45.5% . There was no significant difference in the 100 d survival rate between asymptomatic infected patients and patients diagnosed with adenovirus disease (37.5% vs 22.2% , HR=1.83, 95% CI 0.66-5.04, P=0.24) . Conclusion: The age of >30 years was a risk factor for adenovirus disease. Mortality was high in patients with adenovirus infection after allogeneic hematopoietic stem cell transplantation.

Establishment of a risk model for severe adenovirus pneumonia and prospective study of the timing of intravenous immunoglobulin therapy in children / 中国当代儿科杂志

OBJECTIVES@#To develop a risk prediction model for severe adenovirus pneumonia (AVP) in children, and to explore the appropriate timing for intravenous immunoglobulin (IVIG) therapy for severe AVP.@*METHODS@#Medical data of 1 046 children with AVP were retrospectively analyzed, and a risk prediction model for severe AVP was established using multivariate logistic regression. The model was validated with 102 children with AVP. Then, 75 children aged ≤14 years who were considered at risk of developing severe AVP by the model were prospectively enrolled and divided into three groups (A, B and C) in order of visit, with 25 children in each group. Group A received symptomatic supportive therapy only. With the exception of symptomatic supportive therapy, group B received IVIG treatment at a dose of 1g/(kg·d) for 2 consecutive days, before progressing to severe AVP. With the exception of symptomatic supportive therapy, group C received IVIG treatment at a dose of 1 g/(kg·d) for 2 consecutive days after progressing to severe AVP. Efficacy and related laboratory indicators were compared among the three groups after treatment.@*RESULTS@#Age<18.5 months, underlying diseases, fever duration >6.5 days, hemoglobin level <84.5 g/L, alanine transaminase level >113.5 U/L, and co-infection with bacteria were the six variables that entered into the risk prediction model for severe AVP. The model had an area under the receiver operating characteristic curve of 0.862, sensitivity of 0.878, and specificity of 0.848. The Hosmer-Lemeshow test showed good consistency between the predicted values and the actual observations (P>0.05). After treatment, group B had the shortest fever duration and hospital stay, the lowest hospitalization costs, the highest effective rate of treatment, the lowest incidence of complications, the lowest white blood cell count and interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10 levels, and the highest level of tumor necrosis factor alpha (P<0.05).@*CONCLUSIONS@#The risk model for severe AVP established in this study has good value in predicting the development of severe AVP. IVIG therapy before progression to severe AVP is more effective in treating AVP in children.

Influencia de la seropositividad contra adenovirus-36 sobre riesgo de obesidad y resistencia a la insulina en población infanto-juvenil de la Región de la Araucanía / Influence of adenovirus 36 seropositivity on the risk of obesity and insulin resistance in a population of children and adolescents from the Región de la Araucanía

La infección previa por el adenovirus-36 (Ad-36) se ha asociado con el proceso adipogénico y el control glicémico en modelos experimentales de cultivos celulares y animales. En humanos, la presencia de anticuerpos contra Ad-36 ha mostrado aumentar el riesgo de obesidad y, paradójicamente, mejorar el control glicémico en diferentes poblaciones. Se evaluó la influencia de la seropositividad contra Ad-36 sobre riesgo de obesidad, el perfil lipídico y glicémico en una población de niños en edad escolar. Métodos: Doscientos ocho individuos de entre 9 y 13 años se agruparon según estado nutricional como normopeso (IMC z-score de -1 a +1), con sobrepeso (IMC z-score de +1 a +2) y con obesidad (IMC z-score > +3). Se evaluaron medidas antropométricas, desarrollo puberal según Tanner y parámetros bioquímicos (perfil lipídico, glucemia e insulina) y la seropositividad contra Ad-36. Se determinó la resistencia a la insulina (RI) según criterio para la población infantil chilena. La seropositividad contra Ad-36 se determinó mediante ELISA. Resultados: Hubo una alta prevalencia de sobrepeso/obesidad en la población de estudio. La seropositividad contra Ad-36 fue del 5,4% en el grupo total, pero no se observó una asociación con el estado nutricional. No se encontró correlación entre la seropositividad contra Ad-36 y los parámetros del perfil lipídico. La insulina y la HOMA-RI fueron significativamente más bajas en el grupo Ad-36 (+) (p<0,001), no habiendo sido reportados casos de RI en el grupo Ad-36 (+) en nuestra población. Conclusiones: Nuestros resultados sugieren que la infección previa por el adenovirus-36 afecta la secreción de insulina y la resistencia a la insulina, como se ha descrito anteriormente, sin embargo, no se observa correlación con el desarrollo de la obesidad infantil en la población pediátrica del sur de Chile.

Previous infection with Adenovirus-36 (Ad-36) has been associated with adipogenic process and glycemic control in experimental models of cell culture and animals. In humans, the presence of antibodies against Ad-36 has been shown to increase the risk of obesity and, paradoxically, improve glycemic control in different populations. The influence of Ad-36 seropositivity on obesity risk, lipid and glycemic profile was evaluated in a population of school-age children. Methods: Two hundred eight individuals aged 9 to 13 years were grouped according to their nutritional status as normal weight (BMI z-score from -1 to +1), overweight (BMI z-score from +1 to +2) or obese (BMI z-score from -1 to +1). z-score > +3). Anthropometric measurements, pubertal development according to Tanner stage, biochemical parameters (lipid profile, glycemia and insulin) and seropositivity against Ad-36 were evaluated. Insulin resistance (IR) was determined according to criteria for the Chilean child population. Seropositivity against Ad-36 was determined by ELISA. Results: There was a high prevalence of overweight/obesity in the study population. Seropositivity against Ad-36 was 5.4% in the total group, but no association with nutritional status was observed. No correlation was found between Ad-36 seropositivity and lipid profile parameters. Insulin and HOMA-RI were significantly lower in the Ad-36 (+) group (p<0.001), and no cases of RI were reported in the Ad-36 (+) group in our population. Conclusions: Our results suggest that previous adenovirus-36 infection affects insulin secretion and insulin resistance, as previously described, however, no correlation is observed with the development of childhood obesity in the pediatric population. from southern Chile.

Infección grave diseminada por adenovirus en receptores de trasplante hepático / Severe adenovirus infections in hepatic transplant recipients / Infecção grave por adenovírus disseminado em receptores de transplante de fígado

Resumen: Los adenovirus humanos continúan siendo un desafío en la práctica clínica, se trata de virus de tipo ADN, con amplia distribución en la población, causa frecuente de enfermedad autolimitada en niños. Sin embargo, en pacientes inmunosuprimidos, principalmente trasplantados de células hematopoyéticas y de órganos sólidos, puede llegar a ser causa de enfermedad diseminada severa, con elevada morbimortalidad. Compartimos el primer reporte nacional de enfermedad por adenovirus diseminado, en el que se presentan dos casos clínicos de pacientes trasplantados hepáticos, que desarrollan enfermedad diseminada grave por adenovirus. Se realiza una revisión de la literatura sobre el tema.

Abstract: Human adenoviruses still constitute a challenge in the clinical practice. These are DNA viruses that are widely disseminated among the population and often cause self-limiting diseases in children. However, it may result in a severe diseminated disease with high morbi-mortality rates in immunocompromised patients, in particular transplant recipients of hematopoietic cells and solid organs. The study shares the first national report for disseminated adenovirus disease, presenting two clinical cases of hepatic transplant recipients who developed severe disseminated adenovirus disease. And conducting a literature review on the topic.

Resumo: Os adenovírus humanos continuam sendo um desafio na prática clínica; são vírus do tipo DNA, com ampla distribuição na população, causa frequente de doença autolimitada em crianças. Entretanto, em pacientes imunossuprimidos, principalmente receptores de transplante de células hematopoiéticas e órgãos sólidos, pode se tornar causa de doença disseminada grave, com alta morbimortalidade. Este é o primeiro relato nacional de doença de adenovírus disseminado, no qual são apresentados dois casos clínicos de pacientes transplantados de fígado que desenvolvem doença de adenovírus disseminada grave. Realizou-se também revisão da literatura sobre o assunto.

Gravedad de infecciones respiratorias agudas bajas por adenovirus en los años 2015 y 2016 en el hospital de niños Roberto del Rio / Severity of acute lower respiratory infections due to adenovirus in the years 2015 and 2016 at the Roberto del Rio children's hospital

OBJETIVO. Comparar la gravedad de las infecciones respiratorias agudas bajas (IRAb) producidas por Adenovirus (ADV) entre los años 2015 y 2016, en el Hospital de Niños Roberto del Río. MÉTODOS. Se identificó a pacientes hospitalizados por IRAb por ADV, y se registró edad, sexo, días de hospitalización, ingreso a unidad de paciente crítico (UPC), necesidad de ventilación mecánica (VM), entre otros. Se comparó la evolución de los pacientes, y se analizó la relación entre gravedad y presencia de infecciones asociadas a atención de salud (IAAS). RESULTADOS. Se identificó 158 pacientes hospitalizados por IRAb por ADV. La relación hombre: mujer fue 6:4, con una edad promedio de 17.4 meses. La media de días de hospitalización fue de 9.88 el 2015 y 16.06 el 2016 (p=0.01). El promedio de días de oxigenoterapia fue de 5.86 el 2015 y 8.76 el 2016. Un 22.8% (n:36) de los pacientes ingresó a UPC, y el 20.25% (n:32) requirió VM. Un 41.8% de los casos (n:66) correspondió a IAAS. 3 pacientes fallecieron. CONCLUSIONES. Durante el 2016 hubo hospitalizaciones más prolongadas en comparación al 2015, sin diferencias estadísticamente significativas en relación a requerimientos de oxigenoterapia, VM y fallecimiento. La prolongación de la hospitalización se podría asociar a mayor presencia de IAAS.

OBJETIVE. To compare the severity of lower respiratory infections produced by Adenovirus between 2015 and 2016 at the Hospital de Niños Roberto del Río. METHODS. We identified patients hospitalized for lower respiratory tract infection for ADV and we recorded age, sex, days of hospitalization, admission to Intensive Care Unit (ICU), need for mechanical ventilation (MV), among others. The evolution of the patients between the two years were compared. The relationship between severity and the presence of nosocomial infections was also analyzed. RESULTS. We identified 158 hospitalized patients for ADV. The male:female ratio was 6:4, with an average age of 17.4 months. The mean of hospitalization days was 9.88 days in 2015 and 16.06 days in 2016 (p = 0.01). The average number of oxygen therapy days was 5.86 in 2015 and 8.76 in 2016. The 22.8% (n: 36) of cases required admission in the ICU, and 20.25% (n: 32) required MV. The 41.8% (n: 66) of cases corresponded to nosocomial infections. 3 patients died. CONCLUSIONS. During 2016, there were longer hospitalizations for adenovirus infections compared to 2015, without significant differences in relation to oxygen therapy, MV requirements and death. The prolongation of the hospitalization could be associated by the greater presence of nosocomial infections.

Clinical features of / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of @*METHODS@#A retrospective analysis was performed on the medical data of 228 children with MPP alone and 28 children with MPP and ADV infection. The two groups were compared in terms of clinical features, laboratory results, and treatment outcome.@*RESULTS@#Compared with the MPP group, the MPP+ADV group had significantly longer duration of fever and length of hospital stay, a significantly higher proportion of patients with severe lesions (erosion and exfoliation) of the airway mucosa under bronchoscopy, a significantly higher clinical pulmonary infection score, and a significantly higher proportion of patients requiring oxygen therapy (@*CONCLUSIONS@#Compared with children with MPP alone, children with MPP and ADV infection tend to have more severe clinical manifestations and airway mucosal lesions and are more likely to require oxygen therapy, but most of the laboratory markers lack specificity.

Interpretación de biomarcadores en pacientes pediátricos con infección por Adenovirus / Interpretation of biomarkers in pediatric patients with Adenovirus infection

RESUMEN Objetivo: Evaluar el uso de los biomarcadores proteína C reactiva (PCR) y procalcitonina (PCT) para la valoración de severidad clínica en pacientes pediá-tricos diagnosticados con infección por adenovirus. Método: Se estudiaron 100 pacientes mayores de 28 días y menores a 15 años con diagnóstico confir-mado de infección por adenovirus, en el Hospital Vozandes Quito, Hospital Metropolitano y Hospital de los Valles en el periodo enero 2010 a mayo 2019, se recolectó información demográfica y clínica de forma retrospectiva. las características clínicas y biomarcadores se compararon de acuerdo a la severidad de la patología respiratoria presentada, cuya clasificación por requerimientos terapéuticos la definió como leve, moderada y grave. Resultados: El 89% de los pacientes presentó severidad clínica leve, el 11% moderada y ninguno fue clasificado como severa. El 35% de los pacientes presentaron coinfección con al menos un virus adicional, estos presentaron severidad clínica moderada en el 63,3%. Los valores promedio de PCR fueron 61,3 ± 54,06 mg/L y PCT 0,65 ± 0,8ng/mL. Entre los pacientes con severidad clínica leve y moderada vemos que PCR y PCT fueron superiores en pacientes con severidad clínica leve 66,07±55,09 mg/L vs 22,71±19,60 mg/L, p=0,003 y 0,70±0,83 ng/mL vs 0,23±0,26 ng/mL, p=0.005 respectivamente. Al momento de predecir la severidad clínica de los pacientes pediátricos diagnosticados con adenovirus el área bajo la curva encontrada en estos dos parámetros fue 0,241 y 0,224 para PCT y PCR respectivamente, con valores de sensibilidad y especificidad bajo el 50%. Conclusión: Los biomarcadores PCT y PCR presentan limitada utilidad al momento de predecir la severidad clínica de los pacientes pediátricos diagnosticados con infección por adenovirus.

ABSTRACT Objective: To evaluate the use of C-reactive protein (CRP) and procalcitonin (PCT) biomarkers for the assessment of clinical severity in pediatric patients diag-nosed with adenovirus infection. Method: 100 patients older than 28 days and younger than 15 years with a confirmed diagnosis of adenovirus infection were studied at the Hospital Vozandes Quito, Hospital Metropolitano and Hospital de los Valles in the period January 2010 to May 2019, demographic information was collected and retrospectively. the clinical characteristics and biomarkers were compared according to the severity of the respiratory pathology presented, whose classification by therapeutic requirements defined it as mild, moderate and severe. Results: 89% of the patients presented mild clinical severity, 11% moderate and none were classified as severe. 35% of the patients presented coinfection with at least one additional virus, these presented moderate clinical severity in 63.3%. Mean CRP values were 61.3 ± 54.06 mg / L and PCT 0.65 ± 0.8ng / mL. Among patients with mild and moderate clinical severity, we see that CRP and PCT were higher in patients with mild clinical severity 66.07 ± 55.09 mg / L vs 22.71 ± 19.60 mg / L, p = 0.003 and 0, 70 ± 0.83 ng / mL vs 0.23 ± 0.26 ng / mL, p = 0.005 respectively. When predicting the clinical severity of pediatric patients diagnosed with adenovirus, the area under the curve found in these two parameters was 0.241 and 0.224 for PCT and CRP, respectively, with sensitivity and specificity values below 50%. Conclusion: PCT and CRP biomarkers have limited usefulness when predicting the clinical severity of pediatric patients diagnosed with adenovirus infection

Estudio clínico-epidemiológico de las infecciones respiratorias agudas bajas causadas por adenovirus en niños hospitalizados. Diecinueve años de vigilancia epidemiológica activa / Clinical and epidemiological study of acute lower respiratory tract infections caused by adenovirus in hospitalized children. Nineteen years of active epidemiological surveillance

Introducción. La infección respiratoria aguda baja por adenovirus es una importante causa de morbimortalidad en niños. Objetivos: Describir el patrón clínico-epidemiológico y los factores asociados en niños hospitalizados.Métodos. Estudio transversal en niños ingresados por infección respiratoria aguda baja al Hospital de Niños Ricardo Gutiérrez, Buenos Aires, en 2000-2018. El diagnóstico viral se realizó mediante inmunofluorescencia indirecta en secreciones nasofaríngeas. Se compararon características clínico-epidemiológicas de infección por adenovirus con otros virus respiratorios (virus sincicial respiratorio, influenza y parainfluenza). Se utilizó regresión logística múltiple para identificar predictores independientes de infección.Resultados. De 16018 pacientes con infección respiratoria aguda baja, 13545 fueron testeados para virus respiratorios y 6047 (el 45 %) fueron positivos. Adenovirus fue el agente menos frecuente [el 4,4 % (265) de los casos]; presentó una tendencia en descenso durante todo el período estudiado (pico en 2003) y circuló durante todo el año (pico en julio). El 63,8 % eran varones; mediana de edad: 11 meses (rango intercuartílico: 6-20). La presentación clínica más frecuente fue neumonía (el 63 %). El 50 % tenía internaciones previas por causa respiratoria; el 15,6 % eran reingresos; el 58,3 % tenía comorbilidades. El 19,2 % requirió asistencia ventilatoria; el 44 %registró complicaciones. La letalidad fue del 7,7 %. La infección por adenovirus se asoció a edad ≥ 12 meses, sexo masculino, presentación clínica de neumonía, internaciones previas por causas respiratorias y reinternaciones.Conclusiones. Los adenovirus fueron detectados con menor frecuencia que los otros virus respiratorios, aunque presentaron un importante perfil de morbimortalidad

Introduction. Acute lower respiratory tract infection (ALRTI) caused by adenovirus is a major cause of morbidity and mortality in children.Objectives. To describe the clinical and epidemiological pattern and associated factors in hospitalized children.Methods. Cross-sectional study in children admitted due to ALRTI to Hospital de Niños "Ricardo Gutiérrez," in the Autonomous City of Buenos Aires, between 2000 and 2018. Viral diagnosis was done by indirect immunofluorescence in nasopharyngeal secretions. The clinical and epidemiological characteristics of adenovirus infection were compared to other respiratory viruses (respiratory syncytial virus, influenza, and parainfluenza). A multiple logistic regression was done to identify independent predictors of infection.Results. Out of 16 018 patients with ALRTI, 13 545 were tested for respiratory viruses; 6047 (45 %) had a positive result. Adenovirus was the least common agent (4.4 % [265] of cases); it tended towards a reduction over the study period (peak in 2003) and circulated throughout the year (peak in July). In total, 63.8 % of patients were males; median age: 11 months (interquartile range: 6-20). The most common clinical presentation was pneumonia (63 %). Prior admissions due to respiratory conditions were seen in 50 %; 15.6 %were readmissions; 58.3 % had comorbidities. Ventilatory support was required by 19.2 %and complications were recorded in 44 %. The fatality rate was 7.7 %. Adenovirus infection was associated with age ≥ 12 months, male sex, clinical presentation of pneumonia, prior admissions due to respiratory conditions, and readmissions.Conclusions. Adenoviruses were less common than other respiratory viruses, although their morbidity and mortality were important

Clinical features of children with severe adenovirus pneumonia and hemophagocytic syndrome: an analysis of 30 cases / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of children with severe adenovirus pneumonia (SAP) and hemophagocytic syndrome (HPS).@*METHODS@#A retrospective analysis was performed from the chart review data of 30 children with SAP and HPS who were admitted from January 2014 to June 2019. According to the prognosis, the children were divided into a good prognosis group (n=18) and a poor prognosis group (n=12).@*RESULTS@#Among the 30 children with SAP and HPS, the ratio of male to female was 2:1. The median age of onset was 1 year and 3 months (range 3 months to 5 years), and the mean course of fever was 19±7 d. Of the 30 children, 28 (93%) experienced disease onset in January to June. High-throughput gene detection of serum pathogens showed that 16 (53%) children were positive for human adenovirus type 7 (HAdV-7), and the other 14 (47%) children were positive for HAdV antigen based on immunofluorescence assay for throat swab, with unknown type. Of all 30 children, 29 (97%) had respiratory complications, 24 (80%) had cardiovascular complications, 16 (53%) had gastrointestinal complications, and 9 (30%) had toxic encephalopathy. Eighteen children (60%) improved or recovered and 12 (40%) did not recover (3 died). Compared with the good prognosis group, the poor prognosis group had a significantly longer course from onset to diagnosis of HPS (P<0.05), significantly higher levels of fibrinogen and tumor necrosis factor-α (P<0.05), and a significantly lower level of interferon-γ (P<0.05). The mean follow-up time was 6±2 months; 11 (41%) children recovered, 1 (4%) experienced recurrence of HPS, and 15 (56%) had the sequela of post-infectious bronchiolitis obliterans (PIBO).@*CONCLUSIONS@#HPS may be observed in children with SAP, and PIBO is the most common sequela of SAP.

Fatal nosocomial hemorrhagic enterocolitis probably caused by adenovirus: report of one case / Enterocolitis hemorrágica fatal nosocomial probablemente causada por adenovirus: informe de un caso

ABSTRACT Adenovirus (ADV) is a recognized cause of severe disease among immunocompromised patients. We report a previously healthy 39-year-old female, admitted with influenza pneumonia and evolving with lung hemorrhage and acute renal failure requiring mechanical ventilation and hemodialysis. She received high corticosteroid doses due to an initial suspicion of alveolar hemorrhage. Lymphopenia already present before steroid use (567/μL), was maintained during the whole hospital stay (mean 782/μL). From the second week of admission she presented a high-volume diarrhea (mean 2.5 L/day) associated to intermittent bloody stools. An ulcerative enterocolitis was confirmed by CT images and colonoscopy. ADV was detected in a colonic tissue sample by real time PCR but not by a commercial filmarray test. Cidofovir-probenecid and racecadotril therapy were indicated without changing the clinical course of diarrhea and the patient finally died.

Adenovirus (ADV) es una causa reconocida de enfermedades graves en pacientes inmunocomprometidos. Informamos el caso de una mujer de 39 años, previamente sana, que ingresó por neumonía grave por influenza, evolucionando con hemorragia pulmonar y falla renal aguda, requiriendo ventilación mecánica y hemodiálisis. Recibió altas dosis de corticoides por la sospecha inicial de una hemorragia alveolar. Tuvo linfopenia durante toda su estadía (promedio 782/μL), la que ya estaba presente antes del uso de los corticoides (567/μL). Desde la segunda semana de hospitalización, presentó una diarrea de alto volumen (promedio 2,5 L/día) asociada a la presencia de sangre en deposiciones en forma intermitente. Se confirmó una enterocolitis ulcerativa por tomografía computada y colonoscopía. Se detectó ADV en muestras de biopsia colónica por PCR en tiempo real pero no por un test de PCR múltiples automatizado comercial. Fue tratada con cidofovir-probenecid y racecadrotrilo sin impacto clínico y la paciente finalmente falleció.

Research progress on early identification of severe adenovirus pneumonia in children / 浙江大学学报·医学版

Severe adenovirus pneumonia has a high mortality and incidence of sequelae. Fever and cough are the main symptoms of children's severe adenovirus pneumonia, but such clinical manifestations are lack of specificity. For children with persistent high fever who are in the epidemic age and season, the adenovirus etiology detection, blood routine, cytokines, T cell subsets and imaging examinations are suggested. Children with early manifestations of infiltration of lung segment and lobar parenchyma, obvious emphysema, interstitial pneumonia or a large amount of pleural effusion should be alerted to have severe adenovirus pneumonia. This article reviews the epidemiological characteristics and risk factors of adenovirus pneumonia in different seasons, regions and serology, and the laboratory findings and imaging features of severe adenovirus pneumonia, which would be helpful for the early identification of the disease.

Detection of bluetongue virus in Brazilian cervids in São Paulo state / Detecção de vírus da língua azul em cervídeos brasileiros no estado de São Paulo

Viral hemorrhagic diseases in cervids occur worldwide and include epizootic hemorrhagic disease (EHD), bluetongue (BT), and adenoviral hemorrhagic disease (AHD). Since gross lesions in all three hemorrhagic diseases are identical (hemorrhagic enteropathy, pulmonary edema, systemic petechial and suffusion hemorrhages), it is necessary to use accurate techniques for a definitive etiologic diagnosis. Archival material (paraffin blocks) at the Department of Veterinary Pathology of FCAV - Unesp was reviewed for lesions of hemorrhagic disease and 42 captive and free-living Brazilian deer were selected to include in this study. Paraffin-embedded tissues were evaluated using immunohistochemistry and tested negative for adenovirus. Using real time RT-PCR, EHD virus was not detected in paraffin-embedded tissues in any of the cases evaluated. The same technique was used for detection of BT virus and seven positive animals (16,66%) were confirmed after agarose 4% gel electrophoresis and gene sequencing. The main macroscopic changes observed in the positive animals were hemorrhagic intestinal contents, reddish mucous membrane of the gastrointestinal tract, ulcers on tongue and petechiae in various organs. Microscopic changes observed were lymphocytic inflammatory infiltrate in liver, kidney and lungs, hemorrhage, and congestion in various organs. All positive cases were from captive animals, three females (two young and one adult), and four young males. This study demonstrates that the bluetongue virus is involved in hemorrhagic disease outbreaks of deer in Brazil.(AU)

Doenças hemorrágicas virais em cervídeos ocorrem no mundo todo e incluem a doença epizoótica hemorrágica (DEH), língua azul (LA), e doença hemorrágica por adenovírus (DHA). Uma vez que as lesões nas três doenças hemorrágicas são idênticas (enteropatia hemorrágica, edema pulmonar, petéquias sistêmicas e sufusões hemorrágicas), é necessário utilizar técnicas precisas para um diagnóstico etiológico definitivo. Material de arquivo (blocos de parafina) do Departamento de Patologia Veterinária da FCAV - Unesp foi revisado para lesões de doenças hemorrágicas e 42 cervídeos brasileiros de cativeiro e de vida livre foram selecionados e incluídos neste estudo. Tecidos embebidos em parafina foram avaliados usando imunohistoquímica e foram negativos para adenovírus. Usando o RT-PCR em tempo real, o vírus da DEH não foi detectado nos tecidos de nenhum dos casos avaliados. A mesma técnica foi utilizada para detecção do vírus da LA e sete animais positivos (16,66%) foram confirmados após eletroforese em gel de agarose a 4% e sequenciamento genético. As principais alterações macroscópicas observadas nos animais positivos foram conteúdo intestinal hemorrágico, mucosa do trato gastrointestinal avermelhada, úlceras na língua e petéquias em vários órgãos. As alterações microscópicas observadas foram infiltrado inflamatório linfocítico em fígado, rins e pulmões, e hemorragia e congestão em vários órgãos. Todos os casos positivos foram de animais de cativeiro, três fêmeas (dois jovens e um adulto), e quatro jovens do sexo masculino. Este estudo demonstra que o vírus da lingual azul está envolvido nos surtos de doença hemorrágica em veados no Brasil.(AU)

Disseminated adenovirus infection in a 10-year-old renal allograft recipient

Disseminated adenovirus infection can result in high mortality and morbidity in immunocompromised patients. Here, we report the case of a 10-year-old renal allograft recipient who presented with hematuria and dysuria. Adenovirus was isolated from his urine. His urinary symptoms decreased after intravenous hydration and reduction of immunosuppressants. However, 2 weeks later he presented with general weakness and laboratory tests indicated renal failure necessitating emergency hemodialysis. Adenovirus was detected in his sputum; therefore, intravenous ganciclovir and immunoglobulin therapy were initiated. Renal biopsy revealed diffuse necrotizing granulomatous tubulointerstitial nephritis compatible with renal involvement of the viral infection. Adenovirus was detected in his serum. Despite cidofovir administration for 2 weeks, adenovirus was also detected in the cerebrospinal fluid, resulting in generalized tonic-clonic seizure. The patient died 7 weeks after the onset of urinary symptoms. Adenovirus should be considered in screening tests for post-renal transplantation patients who present with hemorrhagic cystitis.

Incidence and Sero-survey of Canine Adenovirus Type 2 in Various Animal Species

Canine adenovirus type 2 (CAV-2) is the cause of a major respiratory illness in dogs. In this study, we analyzed adenovirus infections in dogs using 2000–2017 data from the Animal and Plant Quarantine Agency (APQA) and conducted a serological survey of CAV-2 infection in six animal species in Korea. In total, 38 of the 3,179 dog samples were confirmed as canine adenovirus infections. In serological survey, 1,028 dog sera, 160 raccoon dog sera, 100 cattle sera, 257 sow sera, 206 horse sera, and 106 cat sera, collected from January 2016 to July 2018, were screened for the presence of anti-CAV-2 antibodies by virus neutralization test. The seropositivity rates for dogs, raccoon dogs, cattle, sows, horses, and cats were 88.5% (910/1,028), 51.3% (82/160), 85.0% (85/100), 48.6% (125/257), 35.0% (72/206), and 2.8% (3/106), respectively. Among dogs and raccoon dogs, 1.9% (20/1,028) and 8.8% (14/160), respectively, had a virus-neutralizing antibody (VNA) titer of over 1:256. A high CAV-2 VNA titer indicates a repeated vaccination or natural infection in Korean dogs and circulation of CAV-2 in raccoon dog populations.

Discrimination of Kawasaki disease with concomitant adenoviral detection differentiating from isolated adenoviral infection / 소아과

PURPOSE: Human adenovirus infection mimics Kawasaki disease (KD) but can be detected in KD patients. The aim of this study was to determine the clinical differences between KD with adenovirus infection and only adenoviral infection and to identify biomarkers for prediction of adenovirus-positive KD from isolated adenoviral infection. METHODS: A total of 147 patients with isolated adenovirus were identified by quantitative polymerase chain reaction. In addition, 11 patients having KD with adenovirus, who were treated with intravenous immunoglobulin therapy during the acute phase of KD were also evaluated. RESULTS: Compared with the adenoviral infection group, the KD with adenovirus group was significantly associated with frequent lip and tongue changes, skin rash and changes in the extremities. In the laboratory parameters, higher C-reactive protein (CRP) level and presence of hypoalbuminemia and sterile pyuria were significantly associated with the KD group. In the multivariate analysis, lip and tongue changes (odds ratio [OR], 1.416; 95% confidence interval [CI], 1.151–1.741; P=0.001), high CRP level (OR, 1.039; 95% CI 1.743–1.454; P= 0.021) and sterile pyuria (OR 1.052; 95% CI 0.861–1.286; P=0.041) were the significant predictive factors of KD. In addition, the cutoff CRP level related to KD with adenoviral detection was 56 mg/L, with a sensitivity of 81.8% and a specificity of 75.9%. CONCLUSION: Lip and tongue changes, higher serum CRP level and sterile pyuria were significantly correlated with adenovirus-positive KD.

C-reactive protein and N-terminal pro-brain natriuretic peptide discrepancy: a differentiation of adenoviral pharyngoconjunctival fever from Kawasaki disease / 소아과

PURPOSE: To differentiate adenoviral pharyngoconjunctival fever (PCF) from acute Kawasaki disease (KD) using laboratory tests before results of virus-real time polymerase chain reaction and ophthalmologic examination are obtained. METHODS: Baseline patient characteristics and laboratory measurements were compared between 40 patients with adenovirus infection and 123 patients with KD. RESULTS: The patients with adenovirus infection were generally older than those with KD (median: 3.9 years vs. 2 years, P=0.000). White blood cell and, platelet count, and aspartate aminotransferase, alanine aminotransferase, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels showed significant differences between the 2 groups, but the C-reactive protein (CRP) levels did not (6.8±3.0 mg/dL vs. 8.3±5.8 mg/dL, P=0.126). In the adenovirus infection group, the CRP levels were < 1, < 3, < 10, and ≥10 mg/dL in 2 (5%), 3 (7.5%), 30 (75%), and 5 patients (12.5%), respectively. The cutoff NT-proBNP level was 265 pg/mL. Discrepancy was defined as CRP and NT-proBNP levels of ≥3 or < 3 mg/dL, and < 265 or ≥265 pg/mL, respectively. Among the 35 patients with adenovirus infection whose CRP levels were ≥3 mg/dL, 29 (82.9%) showed a discrepancy. Conversely, of the 103 patients with KD whose CRP levels were ≥3 mg/dL, 83 (80.6%) showed no discrepancy. Between the groups, a significant difference in discrepancy rate was observed (P=0.000). None of the patients with adenovirus infection had CRP and NT-proBNP levels of < 3 mg/dL and ≥265 pg/mL, respectively. CONCLUSION: With a sensitivity of 82.9% and a specificity of 80.6%, CRP and NT-proBNP levels may differentiate between adenoviral PCF and acute KD.

Comparison of Clinical Manifestation and Laboratory Findings between Adenoviral Infection with or without Kawasaki Disease / 이화의대지

OBJECTIVES: Adenovirus infection, which has been known to mimic Kawasaki disease (KD), is one of the most frequent conditions observed during differential diagnosis when considering KD. Accordingly, it is essential to being able to differentiate between these two diseases. Therefore, we performed multiplex reverse transcriptase-polymerase chain reaction and tissue-Doppler echocardiography to distinguish between adenovirus patients and KD patients. METHODS: A total of 113 adenoviral infection patients (female 48, male 65) diagnosed from January 2010 to June 2016 were evaluated. We divided adenoviral infection patients into two groups: group 1, which consisted of individuals diagnosed with KD according to the KD American Heart Association criteria (n=62, KD with adenovirus infection); and group 2, which comprised individuals only diagnosed with adenovirus infection (n=51). Laboratory data were obtained from each patient including N-terminal pro-brain natriuretic peptide. Echocardiographic measurements were compared between two groups. In addition, reverse transcriptase-polymerase chain reaction was performed using nasopharyngeal secretions to diagnose adenoviral infection. RESULTS: Conjunctival injection, cervical lymphadenopathy, polymorphous skin rash, abnormalities of the lip or oral mucosa and abnormalities of extremities were significantly higher in group 1 than group 2. Moreover, group 1 had significantly higher C-reactive protein and alanine aminotransferase levels, as well as lower platelet counts and albumin levels than group 2. Coronary artery diameter was significantly greater in group 1 than group 2. CONCLUSION: In patients with adenoviral infection with unexplained prolonged fever, echocardiography and C-reactive protein can be used to differentiate KD with adenoviral infection from adenoviral infection alone.

Development of a prototype immunochromatographic test for rapid diagnosis of respiratory adenovirus infection

Abstract Human adenoviruses comprise an important group of etiologic agents that are responsible for various diseases in adults and children, such as respiratory, ocular, gastroenteric, and urinary infections. In immunocompromised and organ-transplanted individuals, these agents can cause generalized infections. Rapid diagnostic methods for detecting these infectious agents are not widely available.The aim of this work was to produce monoclonal and polyclonal anti-adenovirus antibodies to be used in a rapid diagnostic test for respiratory infections.Adenovirus hexons were satisfactorily purified by ultracentrifugation and chromatography. After virus purification, anti-hexon monoclonal antibodies were produced and characterized, following classical methods. Antibodies were specific for adenoviruses 2, 3, 5, and 41. The proposed immunochromatographic test was standardized using colloidal gold.The standardization of the rapid test was sufficient to detect adenovirus antigens (in nasopharyngeal lavage samples) with sensitivity of 100% and specificity of 85% when compared to direct immunofluorescence.The immunochromatographic assay prototype was sufficiently sensitive to detect B (3), C (2 and 5), and F (41) adenovirus samples. Although based on preliminary data, the test demonstrated the same performance as direct immunofluorescence, but with the advantage of being a point-of-care test. Further studies are still needed to confirm its effectiveness in clinical practice.

Adenovirus 36 y su potencial contribución en el desarrollo de obesidad / The potential contribution of adenovirus 36 to the development of obesity

The evidence of the last 20 years shows a link between viral infections and obesity in animals and humans. There are five adenovirus which have been associated with development of obesity in animals. SMAM-1 virus was the first studied in humans associated with obesity. There is compelling evidence that Ad-36 virus could contribute to the development of obesity in humans and it is related with body mass index (BMI). This manuscript reviews the association between Ad-36 and the other four virus infections with obesity. An electronic search of articles in the databases PubMed and Scielo, with use of key words: obesity, infection, adipose tissue, Ad-36, 3T3-L1 was performed. The search was restricted "human" and "animals". The importance of the relationship between virus infections and obesity has increased over the past two decades. Ad-36 shows more compelling evidence in humans. There are reports involving this virus in the enhancement of adipogenesis, adipocyte differentiation, a lower secretion of leptin and an increased insulin sensitivity. Future work should focus in larger cohort studies to confirm this association, which explains the global obesity epidemic from a new perspective.

Infección por adenovirus en el Hospital de niños Roberto del Río 2016 / Adenovirus infection at the Roberto del Río children's Hospital 2016

En los meses de invierno, las enfermedades respiratorias representan la primera causa de hospitalización en hospitales pediátricos. La mayoría de estas enfermedades son causadas por virus, dentro de los cuales se encuentra el adenovirus (AdV), el cual puede generar infecciones diseminadas graves, secuelantes e incluso letales y se caracteriza por tener una rápida transmisión entre pacientes, generando brotes intrahospitalarios. Se identificó a 54 pacientes hospitalizados con infección por adenovirus en el periodo de marzo-julio del 2016 con una edad promedio de 18,3 meses, de los cuales 23 casos fueron infecciones asociadas a la atención de salud (IIAS) y 2 tuvieron desenlace fatal. Los casos de IIAS, se asociaron a una mayor tasa de hospitalización prolongada (p= <0.01), ingreso a UPC (p= <0.01) y uso de ventilación mecánica (p= <0.01). No se encontró asociación entre la presencia de antecedentes mórbidos con el desarrollo de IIAS. Las IIAS por adenovirus se asocia a una hospitalización prolongada, ingreso de unidades de alta complejidad y necesidad de uso de ventilación mecánica. Dado que el adenovirus se transmite a través de contactos directo, aerosoles y fómites, las medidas básicas de precaución de contacto y de aislamiento permiten reducir los contagios nosocomiales, recayendo la responsabilidad en todo el equipo de salud a cargo.

Respiratorio deseases are frequent in winter times. being the main cause of hospital admissions. Viral infecciones are the main etiology, and adenovirus infección clould lead to severe disease, with cross infections. We identified 54 patients admitted to the Roberto del Río Childrens hospital in 2016, with a mean age of 18,3 months old; 23 cases where nosocomial infection, and 2 were fatal. Hospital acquired adenovirus infection were associated to long hospital stay (p= <0.01), intensive care admission (p= <0.01) and ventilatory support (p= <0.01). We did not find previous illness conditions. Adenovirus hospital acquired infection is associated with longer hospital stay and dead. Adenovirus is transmitted with direct contact, aerosols and fomites, therefore basic contact precautions are important.