Background: Except for influenza pandemics, different observational studies have failed to demonstrate differences in mortality between various etiologies in adult patients hospitalized for respiratory infections. Aim: To compare clinical and mortality differences between different viral pathogens associated with severe acute respiratory infections (SARI) in hospitalized adults. Material and Methods: One-year prospective study in a sentinel center. We included 132 patients with SARI hospitalized for any of the nine viruses under study by PCR. Clinical variables were compared, excluding cases of coinfection. Results: A viral coinfection was identified in 12% and influenza infection in 56% of cases. Eighty percent of patients were aged ≥ 65 years, with a high frequency of comorbidities, 27% were bedridden. Twenty four percent were admitted to critical care units, 20% required ventilatory assistance and 16% died. Cases occurred throughout the year, with an expected seasonal peak between autumn and spring and a predominance of infections not associated with influenza during summer months. In the multivariate analysis, only being bedridden was significantly associated with mortality at discharge (Odds ratio 23.46; 95% confidence intervals 3.33-165.12, p < 0.01), without association with age, comorbidity, viral pathogen involved, laboratory parameters, clinical presentation or CURB65 score. No major clinical dissimilarities were found between different viral pathogens. Conclusions: In our series of patients, mostly elderly, only bedridden status was significantly associated with mortality at discharge in patients hospitalized for SARI. Viral pathogens were not relevant.

Los factores del huésped son más importantes que el tipo viral para predecir el desenlace en pacientes hospitalizados por infecciones respiratoria aguda grave. Exceptuando las pandemias de influenza, diferentes estudios observacionales no han logrado demostrar diferencias en mortalidad entre diferentes patógenos en pacientes adultos hospitalizados por infecciones respiratorias. Objetivo: Comparar diferencias clínicas y en mortalidad entre diferentes patógenos virales asociados a infección respiratoria aguda grave (IRAG) en adultos hospitalizados. Método: Estudio prospectivo durante un año en un centro centinela. Se incluyeron casos de IRAG hospitalizados por alguno de los 9 virus bajo estudio por RCP. Se compararon variables clínicas y desenlace. Resultados: Ingresaron 132 pacientes con IRAG. Se identificó coinfección viral en 12,1% e infección por influenza en 56,1%. La mayor parte era de la tercera edad (80,3%) con una alta frecuencia de comorbilidad y 27,3% estaba postrado. Veintitres coma cinco por ciento ingresó a unidad de cuidados críticos, 19,7% requirió asistencia ventilatoria y 15,9% fallecieron. Los casos ocurrieron todo el año, con un aumento estacional esperado entre otoño y primavera y predominio de infecciones no asociadas a influenza en verano. En el análisis multivariado, sólo la postración se asoció significativamente a mortalidad al egreso (ORa 23,46 IC95 3,33-165,12, p = 0,002), sin asociación con la edad, comorbilidad, patógeno viral involucrado, parámetros de laboratorio, presentación clínica o puntuación CURB65. No se encontraron discordancias clínicas mayores entre diferentes agentes virales. Conclusiones: En nuestra serie de pacientes, mayoritariamente de la tercera edad, sólo la postración se asoció significativamente a mortalidad al egreso en pacientes hospitalizados por IRAG. El patógeno viral no resultó ser relevante.

RESUMO Objetivo Descrever as características clínicas de pacientes adultos com infecção respiratória aguda grave (SARI) associada ao vírus da influenza e analisar os subtipos virais identificados em amostras coletadas destes pacientes, os recursos hospitalares empregados no tratamento clínico, a evolução clínica e os fatores de risco clínicos associados a um desfecho fatal, a partir de dados observacionais da rede de vigilância de SARI (SARInet) no Chile. Métodos Foram identificados os adultos hospitalizados com SARI associada a influenza em um hospital-sentinela de vigilância de SARI, em Santiago, de 1o de julho de 2011 a 31 de dezembro de 2015. A ocorrência de influenza foi confirmada em amostras respiratórias em todos os casos com a reação em cadeia da polimerase via transcriptase reversa (RT-RCP). Resultados Ao todo, 221 pacientes (idade média de 74,1 anos) foram hospitalizados com SARI associada a influenza no período de estudo. Nesta coorte, 91,4% apresentavam fatores de risco para complicação e 34,3% haviam sido vacinados na última campanha de vacinação. Pneumonia foi a manifestação clínica mais frequente, ocorrendo em 57,0% da coorte. Outras manifestações foram doença gripal, bronquite crônica exacerbada, insuficiência cardíaca descompensada e crise asmática. Os casos estiveram distribuídos ao longo do ano, com pico epidêmico no outono–inverno. Houve circulação simultânea dos vírus da influenza A (H1N1pdm09 e H3N2) e B. Leitos de terapia intensiva foram necessários em 26,7% da coorte e suporte ventilatório, em 19,5%. Na análise multivariada, quatro fatores importantes associados à mortalidade hospitalar foram identificados: estar restrito ao leito (odds ratio ajustado [ORaj] 22.3; intervalo de confiança de 95% [IC 95%] 3.0–164); ser admitido na unidade de terapia intensiva (ORaj 8.9, IC 95% 1.4 4–55); relação Pa02/Fi02 <250 (ORaj 5.8; IC 95% 1.02–33) e aumento da creatinina sérica (>1 mg/dl) (ORaj 5.47; IC 95% 1.20–24). A vacinação sazonal contra influenza foi identificada como importante fator de proteção (ORaj 0.14; IC 95% 0.021–0.90). Conclusões A SARI associada a influenza acometeu sobretudo pacientes idosos com doenças preexistentes. A maioria dos pacientes evoluiu com insuficiência respiratória e mais de um quarto precisou de cuidados intensivos. O quadro clínico foi variável. Morte foi associada às características do hospedeiro e problemas relacionados à doença. A vacinação teve efeito protetor e o tipo viral não influiu no desfecho.

ABSTRACT Objective To 1) describe clinical characteristics of adult patients in Chile with severe acute respiratory infections (SARI) associated with influenza viruses, and 2) analyze virus subtypes identified in specimens collected from those patients, hospital resources used in clinical management, clinical evolution, and risk factors associated with a fatal outcome, using observational data from the SARI surveillance network (SARInet). Methods Adults hospitalized from 1 July 2011 to 31 December 2015 with influenza-associated SARI at a SARI sentinel surveillance hospital in Santiago were identified and the presence of influenza in all cases confirmed by reverse transcription polymerase chain reaction (RT-PCR), using respiratory samples. Results A total of 221 patients (mean age: 74.1 years) were hospitalized with influenza-associated SARI during the study period. Of this study cohort, 91.4% had risk factors for complications and 34.3% had been vaccinated during the most recent campaign. Pneumonia was the most frequent clinical manifestation, occurring in 57.0% of the cohort; other manifestations included influenza-like illness, exacerbated chronic bronchitis, decompensated heart failure, and asthmatic crisis. Cases occurred year-round, with an epidemic peak during autumn–winter. Both influenza A (H1N1pdm09 and H3N2) and B virus co-circulated. Critical care beds were required for 26.7% of the cohort, and 19.5% needed ventilatory assistance. Multivariate analysis identified four significant factors associated with in-hospital mortality: 1) being bedridden (adjusted odds ratio (aOR): 22.3; 95% confidence interval (CI): 3.0–164); 2) admission to critical care unit (aOR: 8.9; CI: 1.44–55); 3) Pa02/Fi02 ratio < 250 (aOR: 5.8; CI: 1.02–33); and 4) increased serum creatinine concentration (> 1 mg/dL) (aOR: 5.47; CI: 1.20–24). Seasonal influenza vaccine was identified as a significant protective factor (aOR: 0.14; CI: 0.021–0.90). Conclusions Influenza-associated SARI affected mainly elderly patients with underlying conditions. Most patients evolved to respiratory failure and more than one-quarter required critical care beds. Clinical presentation was variable. Death was associated with host characteristics and disease-associated conditions, and vaccine was protective. Virus type did not influence outcome.

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Acute renal failure (ARF) requiring hemodialysis is not common among patients affected by influenza. We report two unvaccinated adult patients with smoking habit, which were admitted with severe influenza A H1N1pdm09 that evolved with shock and required mechanical ventilation. Both patients developed progressive renal failure with oliguria/anuria, associated with urinary of inflammatory sediment with proteinuria, microhematuria and in one case also with hypocomplementemia, suggesting acute glomerulonephritis. Renal replacement therapy (RRT) was required in both cases. In one patient, who died of late complications, sequencing of the HA1 segment revealed the previously described D222N mutation associated to severe cases. ARF with RRT appears to be an uncommon complication of patients hospitalized for influenza A H1N1pdm09 and may be secondary to acute glomerulonephritis.

La insuficiencia renal aguda (IRA) que requiere hemodiálisis no es una complicación común entre los pacientes afectados por influenza. Se comunican los casos clínicos de dos pacientes adultos fumadores no vacunados, que se internaron por influenza A H1N1pdm09 grave por shock y necesidad de ventilación mecánica. Ambos desarrollaron una falla renal progresiva con oliguria/anuria, asociada a un sedimento de orina inflamatorio con proteinuria, microhematuria y en un caso además con hipocomplementemia, sugiriendo una glomerulonefritis aguda. Se requirió terapia de reemplazo renal (TRR) en ambos casos. En uno de los pacientes, que falleció por complicaciones tardías, la secuenciación del segmento HA1 reveló la mutación D222N previamente descrita en casos graves. La IRA con TRR parece ser una complicación infrecuente de los pacientes ingresados por influenza A H1N1pdm09 y puede ser secundaria a una glomerulonefritis aguda.

Abstract We report the first description of a rare catalase-negative strain of Staphylococcus aureus in Chile. This new variant was isolated from blood and synovial tissue samples of a pediatric patient. Sequencing analysis revealed that this catalase-negative strain is related to ST10 strain, which has earlier been described in relation to S. aureus carriers. Interestingly, sequence analysis of the catalase gene katA revealed presence of a novel nonsense mutation that causes premature translational truncation of the C-terminus of the enzyme leading to a loss of 222 amino acids. Our study suggests that loss of catalase activity in this rare catalase-negative Chilean strain is due to this novel nonsense mutation in the katA gene, which truncates the enzyme to just 283 amino acids.

Human rhinovirus (HRV) is an emerging viral pathogen. Aim: To characterize a group of patients admitted due to infection by this agent in a general hospital in Chile. Methods: Cases were identified by RT-PCR for 1 year through active surveillance of patients admitted with severe respiratory illness. Diagnosis was not available during hospitalization. Thirty-two cases were identified, 90% were ≥60 years old or had co-morbid conditions. Human rhinovirus-related admissions represented 23.7% of hospitalization due to severe acute respiratory infections among adults and ranked second to influenza (37.8%). Patients presented with pneumonia (68.8%), decompensated chronic lung conditions (21.9%), heart failure or influenza-like illness (6.3% each). Admission to intensive or intermediate care units was required by 31.2% and in-hospital mortality reached 12.5%. A CURB-65 score ≥3 was significantly associated to in-hospital mortality (p < 0.05). Most patients received antibiotics (90%). Conclusions: Human rhinovirus infections in elderly patients with co-morbid conditions are associated with hospitalizations, requiring critical or semi-critical antibiotics use. A high CURB-65 score was associated to in-hospital mortality.

Influenza A (H1N1) 2009 infection was an important cause of morbidity and mortality in Chile. Aim: To characterize the clinical pattern of hospitalized patients, identify risk factors associated with ICU admission or death, and evaluate its economic impact. Patients and Methods: Twenty five adult patients admitted to 2 hospitals in the Metropolitan Area from May 2009 to December 2010 with PCR confirmed H1N1 infection were analyzed. Total hospital charges were obtained and, using data of registered cases, expenses for the whole country during the first epidemic wave were estimated. Results: Aill cases presented a risk factor: age over 60 years old (n = 13, 52%), co-morbid conditions (n = 24, 96%) or pregnancy (n = 1, 4%). Pneumonia was present in 64% (n = 16) and 16% (n = 4) had hypotension. Only 6 patients (24%) had a CURB-65 score ≥ 2 and 36% (n = 9) requiring ICU admission. Case fatality rate was 16% (n = 4). By multivariate analysis, diabetes mellitus type 2 was independently associated with ICU admission or death (OR 8.12; IC95 1.11-59.2, p < 0.05). Hospital charges for those admitted to ICU or the intermediate care unit reached US$ 20,304, and US$ 1,262 for those admitted in general wards. We estimated US$ 20 million in hospital charges for influenza related hospitalizations during the first wave for the whole country. Conclusions: A high proportion of patients affected by influenza A (H1N1) 2009 infection required ICU admission during 2009-2010. Case fatality rate associated to this infection was high, and diabetes mellitus type 2 was a risk factor for ICU admission or death. Hospital charges were higher for those admitted in critical care units and represented an important expenditure for Chile during the first wave. The CURB-65 score was inappropriate to recognize patients at risk of hospitalization or ICU admission.

Introducción: La infección por influenza A (H1N1) pandémica representó una importante carga de morbilidad y mortalidad en Chile. Objetivo: Caracterización clínica de pacientes hospitalizados durante los años 2009 y 2010, identificar factores de riesgo asociados con ingreso a UCI o muerte y determinar el impacto económico de esta enfermedad. Pacientes y Métodos: Análisis de las características clínicas y evolución en un grupo de 25 pacientes adultos ingresados a dos hospitales institucionales en la Región Metropolitana confirmados por RPC desde mayo de 2009 a diciembre de 2010. Estudio de gastos hospitalarios y estimación de gasto nacional según registro de casos atendidos desde mayo a agosto de 2009. Resultados. Todos los pacientes presentaron una condición de riesgo: edad > 60 años (n: 13, 52%), co-morbilidad (n: 24, 96%) o embarazo ((n: 1, 4%). El 64% (n: 16) presentó neumonía y 16% tuvieron hipotensión arterial (n: 4). Sólo 6 pacientes (24%) tuvieron puntuación CURB-65 ≥ 2. Un 36% (n: 9) requirió manejo en Unidad de Cuidados Intensivos (UCI) y 4 pacientes fallecieron (16%). Por análisis multivariado, el antecedente de diabetes mellitus tipo 2 se asoció en forma significativa e independiente al ingreso a UCI o a un desenlace fatal (OR 8,12; IC95 1,11-59,2, p < 0,05). El gasto por paciente en aquellos que ingresaron a la UCI o Intermedio alcanzó los US$ 20.304 y US$ 1.262, para los que no ingresaron a estas unidades. Para Chile, se estimó un gasto mínimo de 20 millones de dólares por concepto de hospitalización para los primeros cuatro meses de la pandemia el 2009, asumiendo que 60% ingresó a UCI o Unidades Intermedias. Conclusiones: Una alta proporción de los pacientes afectados por influenza A (H1N1) 2009 requirió ingreso a UCI durante los años 2009-2010. La letalidad de esta infección fue elevada y la diabetes mellitus tipo 2 fue un factor de riesgo para ingreso a UCI o muerte. Los gastos hospitalarios fueron elevados, especialmente en los que ingresaron a unidades críticas. El sistema CURB-65 tiene una baja capacidad para reconocer riesgo de hospitalización o muerte en estos pacientes.

The Chilean Ministry of Health (MINSAL) led an investigation to identify associated factors to human influenza A (H1N1) infection in turkeys from poultry farms, Valparaíso. The Agriculture and Livestock Farming Service (SAG) informed the detection of influenza A (low pathogenicity) in turkeys and the Public Health Institute (ISP) confirmed influenza A (H1N1).The study included 100% of operative wards: 31% presented positive event (influenza A (H1N1)); 60% if considered only reproductive wards. Dissemination and dispersion velocity of 13 wards in 18 days evidenced a continuous common source. Interviews were performed to 89% of workers of whom 20% presented influenza-like disease: 26% from reproductive wards and 4% from raising and rearing farms. Of15 risk factors studied insemination and age in females showed statistically significant RR in low oviposition index wards. A man-bird transmission is proposed, through direct transmission of saliva during manual insemination or indirect transmission through contaminated semen. To the authors, this is the first turkey 2009 influenza H1N1 outbreak detected worldwide,in this case with a documented cloacal transmission path.

El MINSAL lideró una investigación para identificar factores asociados a infección por influenza A(H1N1) en pavos de planteles avícolas, Valparaíso. El Servicio Agrícola Ganadero informó la detección de influenza A (baja patogenicidad) en pavos y el ISP confirmó influenza A(H1N1). El estudio incluyó 100% de los pabellones operativos: 31% presentó evento positivo (influenza A(H1N1); 60% al considerar sólo pabellones de reproducción. La diseminación y velocidad de dispersión de 13 pabellones en 18 días evidenció una fuente común continua. Se entrevistó a 89% de los trabajadores y 20% presentó ETI: 26% de pabellones de reproducción y 4% de granjas de cría y recría. De 15 factores analizados, inseminación y edad de las hembras mostraron RR estadísticamente significativos en los planteles con baja ovipostura. Se plantea transmisión hombre-ave directa por saliva en inseminación manual o transmisión indirecta por semen contaminado. Es el primer brote de influenza A(H1N1) 2009 en pavos detectado en el mundo y que se comprueba vía de transmisión cloacal.

In order to understand the clinical and epidemiological aspects of infection with the AH1N1 influenza virus in Chile, a prospective study in the city of San Felipe was undertaken. It analyses the trends in consultations for respiratory causes in three primary care centers and hospital discharges by comparing data from years 2008 and 2009 until epidemiological week 37.It also includes a study of cases of ILI / SARI (influenza like disease/severe acute respiratory disease) in which viruses were detected by direct immunofluorescence (DIF) of nasopharyngeal aspirates and by real-time polymerase chain reaction in the case of influenza A (H1N1) 2009. A household survey was conducted in those cases with confirmed A (H1N1) infection, to identify contacts and history related to influenza virus transmission. The results indicate that the behavior of the pandemic was similar to that observed in the rest of the country, with an increase in emergency room visits for ILI. The most affected age group was from 5 to 14 years (26.5 per thousand inhabitants) and the least affected 60 years or older (1.2 per thousand). A 2.78% of the cases corresponded to SARI and the fatality rate was 0.11%.

Con el objetivo de conocer los aspectos clínicos y epidemiológicos de la infección por el virus A (H1N1) en Chile, se realizó un estudio prospectivo en la ciudad de San Felipe, lugar donde el brote de influenza se inició tardíamente en relación a otras ciudades del país. Se analizó la tendencia en las consultas por causa respiratorias en tres centros de atención primaria y egresos hospitalarios comparando los años 2008 y 2009 hasta la semana epidemiológica 37, y se realizó un estudio prospectivo de casos de enfermedad tipo influenza/infección respiratoria aguda grave (ETI/IRAG), tomando muestras mediante aspirado nasofaríngeo para detección de virus respiratorios por in-munofluorescencia directa (IFD) e identificación de virus influenza A (H1N1) 2009 por reacción de polimerasa en cadena en tiempo real (RPC-TR). En los pacientes confirmados se hizo una encuesta en visita domiciliaria para identificación de contactos y antecedentes relacionados con la transmisión de la influenza. Los resultados indican que el comportamiento de la pandemia fue similar a lo observado en el resto del país, con aumento de consulta principalmente en los servicios de urgencia; el grupo de edad más afectado fue el de 5 a 14 años (26,5 por mil habitantes), el menos afectado el grupo mayor de 60 años (1,2 por mil habitantes). Un 2,78% de los casos correspondió a IRAG y la tasa de letalidad fue de 0,11%.

Background: Following the announcement of the Influenza A(H1N1) pandemic by the World Health Organization in April 2009, a surveillance program was carried out in Chile to detect the introduction of the virus in the country and to monitor its propagation and impact. Aim: To describe the onset of the outbreak and the genetic characterization of the pandemic H1N1 influenza virus in the first detected cases in Chile. Material and Methods: Analysis of18 clinical samples coming from suspicious patients, received in a National Reference Laboratory. RNA reverse transcription and real time influenza gene DNA amplification was carried out in a 7500 Fast and Step One Real Time PCR Systems of Applied Biosystems and MxPro-Mx3000P thermocycler from Stratagene. Super Script III Platinum One-Step Quantitative RT-PCR was used. Results: The virus was first detected in three persons returning from the Dominican Republic via Panamá and a child from the east zone of Santiago. Genetic characterization of the virus showed that the child was infected by a different variant of the pandemic virus than the three persons returning from the Caribbean. Conclusions: The onset of the Influenza outbreak in Chile apparently carne from two different epidemiological groups. The spread of the virus detected in the voyagers was limited immediately However the virus of the fourth case was found in different regions of Chile.