Long-term outcomes for epidemic viral pneumonia survivors after discharge from the intensive care unit: a systematic review

ABSTRACT Objective To review the long-term outcomes (functional status and psychological sequelae) of survivors of critical illnesses due to epidemic viral pneumonia before the COVID-19 pandemic and to establish a benchmark for comparison of the COVID-19 long-term outcomes. Methods This systematic review of clinical studies reported the long-term outcomes in adults admitted to intensive care units who were diagnosed with viral epidemic pneumonia. An electronic search was performed using databases: MEDLINE®, Web of Science™, LILACS/IBECS, and EMBASE. Additionally, complementary searches were conducted on the reference lists of eligible studies. The quality of the studies was assessed using the Newcastle-Ottawa Scale. The results were grouped into tables and textual descriptions. Results The final analysis included 15 studies from a total of 243 studies. This review included 771 patients with Influenza A, Middle East Respiratory Syndrome, and Severe Acute Respiratory Syndrome. It analyzed the quality of life, functionality, lung function, mortality, rate of return to work, rehospitalization, and psychiatric symptoms. The follow-up periods ranged from 1 to 144 months. We found that the quality of life, functional capacity, and pulmonary function were below expected standards. Conclusion This review revealed great heterogeneity between studies attributed to different scales, follow-up time points, and methodologies. However, this systematic review identified negative long-term effects on patient outcomes. Given the possibility of future pandemics, it is essential to identify the long-term effects of viral pneumonia outbreaks. This review was not funded. Prospero database registration: (www.crd.york.ac.uk/prospero) under registration ID CRD42021190296.

Comparison of two pandemics: H1N1 and SARS-CoV-2

SUMMARY OBJECTIVE: We aimed to compare the clinical, epidemiological, and prognostic features of the H1N1 pandemic in 2009 and the severe acute respiratory syndrome coronavirus 2 pandemic in 2020. METHODS: This retrospective study involved subjects from seven centers that were admitted and found to be positive for H1N1 or COVID-19 real-time polymerase chain reaction test. RESULTS: A total of 143 patients with H1N1 and 309 patients with COVID-19 were involved in the study. H1N1 patients were younger than COVID-19 ones. While 58.7% of H1N1 patients were female, 57.9% of COVID-19 patients were male. Complaints of fever, cough, sputum, sore throat, myalgia, weakness, headache, and shortness of breath in H1N1 patients were statistically higher than in COVID-19 ones. The duration of symptoms until H1N1 patients were admitted to the hospital was shorter than that for COVID-19 patients. Leukopenia was more common in COVID-19 patients. C-reactive protein levels were higher in COVID-19 patients, while lactate dehydrogenase levels were higher in H1N1 ones. The mortality rate was also higher in H1N1 cases. CONCLUSIONS: The severe acute respiratory syndrome coronavirus 2 pandemic is a major public health problem that continues to affect the world with its high rate of contagion. In addition, no vaccines or a specific drug for the benefit of millions of people have been found yet. The H1N1 pandemic is an epidemic that affected the whole world about ten years ago and was prevented by the development of vaccines at a short period. Experience in the H1N1 pandemic may be the guide to prevent the COVID-19 pandemic from a worse end.

H1N1: perfil clínico-epidemiológico de pacientes atendidos em um hospital / H1N1: clinical and epidemiological profile of patients treated in a hospital

Objetivo: Avaliar casos de suspeita de gripe H1N1, bem como comparar aspectos epidemiológicos e clínicos dos pacientes com gripe H1N1 confirmada em relação àqueles não confirmados; analisar os critérios de gravidade clínica com relação à confirmação (ou não) da gripe H1N1 e seu desfecho (mortalidade); e criar um banco de dados para fins de comparação com a literatura nacional e mundial. Métodos: Estudo retrospectivo de coorte transversal realizado no período sazonal (outono e inverno) no ano de 2016. Foram analisados os prontuários, acessíveis e completos, de pacientes com suspeita clínica de H1N1, além daqueles com resultados definidos na sorologia. A partir dos dados coletados, foi elaborada tabela de análise epidemiológica, com informações clínicas, laboratoriais e sorológicas. Resultados: Destacam-se a média das faixas etárias mais acometidas de 48 anos, além dos sintomas mais comuns que foram dispneia, tosse e mialgia; as comorbidades foram hipertensão arterial sistêmica, cardiopatias, diabetes e doença pulmonar obstrutiva crônica. Conclusão: Este trabalho contribuiu com a caracterização do perfil epidemiológico regional e auxiliou na definição de indicadores de diagnóstico e gravidade, além de agregar à literatura conteúdos de caráter relevante. Este estudo está registrado como CAAE 58664016.2.0000.5515 na Plataforma Brasil. (AU)

Objective: To evaluate cases of suspected H1N1 flu, as well as to compare epidemiological and clinical aspects of patients with confirmed H1N1 influenza to those who were not confirmed; to analyze the criteria of clinical severity regarding the confirmation (or not) of H1N1 influenza, and its outcome (mortality); and to create a database to be compared with the national and world literature. Methods: This is a cross-sectional retrospective cohort study, carried out in the seasonal period ( fall/winter) of 2016. Accessible and complete medical records of patients with clinical suspicion of H1N1 were analyzed along with those with defined serology results. Based on the collected data, a table of epidemiological analysis was elaborated with clinical, laboratory and serological information. Results: The mean age of the most affected age groups was 48 years; the most common symptoms were dyspnea, cough and myalgia; and the comorbidities were systemic arterial hypertension, cardiopathies, diabetes, and chronic obstructive pulmonary disease. Conclusion: This work contributed to the characterization of the regional epidemiological profile, and helped in the definition of indicators of diagnosis and severity, besides adding relevant content to the literature. This study is registered as CAAE 58664016.2.0000.5515 at Plataforma Brasil. (AU)

Uso da ventilação não invasiva na SDRA e pneumonia secundária a H1N1: revisão sistemática / Use of non-invasive ventilation in ARDS and secondary pneumonia H1N1: systematic review

INTRODUÇÃO: A influenza A é uma infecção respiratória aguda, associada a epidemias e pandemias, sendo um vírus de comportamento sazonal. O uso precoce da ventilação não invasiva tem se mostrado um tratamento de primeira linha em pacientes com síndrome do desconforto respiratório e pneumonia secundaria a influenza A H1N1, resultando em menores taxas de mortalidade. OBJETIVO: Investigar através de revisão sistemática o uso da ventilação não invasiva em pacientes diagnosticados com Influenza A H1N1, secundário a pneumonia e a síndrome do desconforto respiratório agudo. MATERIAIS E MÉTODOS: Foram realizadas buscas nas bases de dados do Periódicos Capes, Science Direct, SciELO, e Pubmed, selecionandose os estudos desenvolvidos nos últimos 10 anos, não sendo imposta restrição de idiomas para a pesquisa. A qualidade metodológica dos estudos foi apontada utilizando a escala de PEDro. RESULTADOS: 16 estudos preencheram o critério de elegibilidade e foram incluídos neste estudo segundo escore de PEDro. Nove estudos mostraram que o uso da ventilação não invasiva foi eficiente em pacientes de média e baixa hipoxemia, diminuindo a taxa de intubação orotraqueal e doenças associadas, menor permanência hospitalar e menores taxas de mortalidade. CONCLUSÃO: O uso da VNI em pacientes com Síndrome do Desconforto Respiratório Agudo e pneumonia secundária ao vírus influenza A H1N1 mostrou-se relevante na reversão da hipoxemia moderada e leve. Critérios, parâmetros e protocolos bem estabelecidos, torna-se muito útil, juntamente com profissionais experientes e preparados, visando assim uma menor taxa de intubação orotraqueal e doenças associadas, e consequentemente uma menor permanência hospitalar e menores taxas de mortalidade.

INTRODUCTION: Influenza A is an acute respiratory infection, associated with epidemics and pandemics, being a virus with seasonal behavior. Early use of noninvasive ventilation has been shown to be first-line treatment in patients with respiratory distress syndrome and influenza A H1N1 secondary pneumonia, resulting in lower mortality rates. OBJECTIVE: To investigate through a systematic review the use of noninvasive ventilation in patients diagnosed with influenza A H1N1, secondary to pneumonia and acute respiratory distress syndrome. MATERIALS AND METHODS: Searches were carried out in the Capes, Science Direct, SciELO, and Pubmed journals, selecting the studies developed in the last 10 years, with no language restriction for the research. The methodological quality of the studies was indicated using the PEDro scale. RESULTS: 16 studies met the eligibility criteria and were included in this study according to PEDro score. Where 9 studies showed that the use of noninvasive ventilation was efficient in patients with medium and low hypoxemia, decreasing the rate of orotracheal intubation and associated diseases, shorter hospital stay and lower mortality rates. CONCLUSION: The use of NIV in patients with Acute Respiratory Distress Syndrome and influenza A H1N1 secondary pneumonia has been shown to be relevant for reversing moderate and mild hypoxemia. Well-established criteria, parameters and protocols become very useful, along with experienced and prepared professionals, thus aiming at a lower rate of orotracheal intubation and associated diseases, and consequently a shorter hospital stay and lower mortality rates.

Initial chest X-ray findings in pediatric patients diagnosed with H1N1 virus infection / Achados iniciais na radiografia de tórax em uma população pediátrica com diagnóstico de infecção viral por H1N1

Abstract Objective: To evaluate chest X-ray findings in pediatric patients diagnosed with influenza A (H1N1) virus infection. Materials and Methods: We retrospectively reviewed chest X-ray findings in 17 cases of pulmonary infection with the H1N1 virus (in 7 males and 10 females) examined between 2012 and 2016. The mean age of the patients was 14 months (range, 2-89 months). The diagnosis was established on the basis of clinical and radiographic criteria, and the virus was detected by polymerase chain reaction. The radiographic findings were categorized by type/pattern of opacity and by lung zone. The patients were divided into two groups: those not requiring ventilatory support; and those requiring ventilatory support or evolving to death. Results: The abnormality most often seen on chest X-rays was that of peribronchovascular opacities, the majority of which affected less than 25% of the lung, the involvement being bilateral and asymmetric. The lung zone most frequently involved was the middle third, with central and peripheral distribution, without pleural effusion. There was a statistically significant difference between the groups in terms of the symmetry of pulmonary involvement, asymmetric findings predominating in the group that required ventilatory support (p = 0.029). Conclusion: In pediatric patients with H1N1 virus infection, the main alterations on the initial chest X-rays are peribronchovascular opacities, nonspecific alveolar opacities, and consolidations. Although the definitive diagnosis of H1N1 virus infection cannot be made on the basis of imaging characteristics alone, using a combination of clinical and radiographic findings can substantially improve the diagnostic accuracy.

Resumo Objetivo: Avaliar os achados na radiografia de tórax de pacientes com diagnóstico de infecção pelo vírus influenza. Materiais e Métodos: Revisamos, retrospectivamente, os achados na radiografia de tórax de 17 casos de infecção pulmonar pelo vírus influenza (7 do sexo masculino e 10 do sexo feminino; idade média de 14 meses, variação de 2 a 89 meses). Os pacientes foram examinados entre 2012 e 2016 e o diagnóstico foi estabelecido por critérios clinicorradiológicos e detecção do vírus por reação em cadeia de polimerase. Os achados radiológicos foram caracterizados por tipo e padrão de opacidade e distribuição por zonas pulmonares. A população estudada foi dividida em dois grupos: sem suporte ventilatório e com suporte ventilatório e/ou óbito. Resultados: A anormalidade encontrada com maior frequência na radiografia de tórax foram as marcas peribroncovasculares, a maioria delas com extensão menor de 25% do pulmão, envolvimento bilateral e assimétrico. A região mais frequentemente envolvida foi o terço médio, com distribuição central e periférica e ausência de derrame pleural. Houve diferença estatisticamente significante na simetria do envolvimento pulmonar, entre os grupos, havendo preponderância de achado assimétrico (p = 0,029) no grupo que necessitou de suporte ventilatório. Conclusão: Pacientes pediátricos com infecção pelo H1N1 apresentam como alterações principais na radiografia do tórax inicial marcas peribroncovasculares, opacidades alveolares inespecíficas e consolidações. Embora o diagnóstico definitivo não possa ser feito com base em imagens características isoladas, uma combinação dos achados clínicos e radiográficos pode melhorar substancialmente a acurácia do diagnóstico nessa doença.

Interesting post-mortem findings in a H1N1 influenza-positive pneumonia patient

Reports of histopathological findings in a patient infected with H1N1 influenza virus are limited in the literature, although many deaths have occurred because of this viral infection. In an otherwise healthy individual with no underlying co-morbid conditions, this virus passes off as a very mild disease. However, it can be fatal in the presence of underlying risk factors. Here, we present the autopsy findings of a patient who died of H1N1 infection, but who was apparently healthy with no predisposing ailments. The autopsy revealed chronic kidney disease and caseating granulomatous lymphadenitis in addition to the known classical diffuse alveolar damage picture seen in this condition. These underlying co-morbidities may provide greater insight and a better understanding of this infection.

Fatores associados ao óbito dos casos graves de influenza A(H1N1)pdm09 / Factors associated with death of severe cases of influenza A(H1N1)pdm09

Resumo Introdução A primeira pandemia de influenza do século XXI ocorreu em 2009, causada pelo novo subtipo de vírus da gripe, o vírus influenza A(H1N1)pdm09. Objetivo Analisar os fatores associados ao óbito por Síndrome Respiratória Aguda Grave (SRAG) por influenza A(H1N1)pdm09 em residentes do município do Rio de Janeiro. Método Análise de dados secundários, incluindo 1.191 casos confirmados para influenza A(H1N1) com critério clínico para SRAG, residentes no município do Rio de Janeiro, em 2009. Análise estatística descritiva e regressão logística para estudo dos fatores associados ao óbito. Resultados 60,3% ocorreram em mulheres, sendo 185 gestantes; 48,1% em menores de 20 anos; 35,7% tinham comorbidades; 91,4% foram hospitalizados; 7,4% foram a óbito. Observou-se maior chance de óbito associada à baixa escolaridade, à presença de comorbidade, ao padrão radiológico de infiltrado intersticial, consolidação ou misto, à confirmação laboratorial e ao estado vacinal contra gripe ignorado. Conclusão Indivíduos com baixa escolaridade, com pelo menos uma comorbidade e com comprometimento pulmonar com um padrão radiológico com infiltrado intersticial, consolidação ou misto tiveram maior chance de evolução a óbito. O melhor conhecimento desse perfil permite um planejamento mais eficiente da assistência à saúde dos pacientes.

Abstract Introduction the first influenza pandemic of the 21st century occurred in 2009, caused by the new subtype of influenza virus, influenza A (H1N1) pdm09. Objective to analyze the factors associated with death due to Severe Acute Respiratory Infection (SARI) caused by influenza A (H1N1) pdm09 in residents of the city of Rio de Janeiro. Method Analysis of secondary data, including 1,191 confirmed cases of influenza A (H1N1) pdm09 with clinical criteria for SARI, residents of the city of Rio de Janeiro, in 2009. Descriptive statistical analysis and logistic regression for the study of factors associated with death. Results 60.3% occurred in women, with 185 pregnant women; 48.1% in children under 20 years old; 35.7% had comorbidities; 91.4% were hospitalized, and 7.4% died. There was a higher chance of death associated with low educational level, presence of comorbidity, radiological pattern of interstitial infiltrate, consolidation or mixed; laboratory confirmation; vaccination status ignored. Conclusion individuals with low educational level who had at least one comorbidity and had pulmonary involvement with a radiological pattern with interstitial infiltrate, consolidation or mixed had a higher chance of dying. Knowledge of this profile allows for more efficient planning of health care.

Clinical analysis of seven cases of H1N1 influenza-associated encephalopathy in children / 中华儿科杂志

Objective@#To investigate the clinical manifestations, diagnosis, and treatment of H1N1 influenza A-associated encephalopathy (IAE) in children.@*Methods@#The clinical manifestations, laboratory tests, cranial magnetic resonance imaging (MRI), electroencephalography (EEG) examinations and treatments of seven children with H1N1 IAE hospitalized in Guangzhou Women and Children′s Medical Center from December 2018 to January 2019 were retrospectively analyzed.@*Results@#Five of the seven children with H1N1 IAE were female. The age at admission was 4 years and 5 months (range 7 months-9 years). Neurological symptoms occurred simultaneously or early (0-3 days) after the flu-like symptom appeared. The main clinical manifestations of neurological symptoms were seizures (repeated seizures in five cases and status convulsion in two cases, including one case of unexpected fever and repeated seizures in a nine-year old girl) accompanied with altered consciousness (drowsiness in five cases and coma in two cases). Cranial MRI in three cases displayed multifocal lesions, mainly in the bilateral thalamus, brainstem and cerebellar hemisphere. MRI also showed reversible splenial lesion in the corpus callusumin in three cases. EEG tracings were characterized by diffuse slow wave activity in four cases, and status epilepticus was monitored in one case. All the 7 cases were treated with oral oseltamivir. Three cases were treated with pulsed methylprednisolone and intravenous immunoglobulin. One case was treated with intravenous immunoglobulin alone and all the patients received oral oseltamivir. All the patients survived, with three patients had minor neurological sequelae at discharge.@*Conclusions@#The main clinical manifestations of H1N1 IAE are seizures and altered consciousness. Cranial MRI combined with EEG is helpful for early diagnosis. Intravenous immunoglobulin and (or) methylprednisolone should be considered for severe cases.

A case report of H1N1 severe pneumonia treated with mechanical ventilation in the prone position / 天津医药

@#Acute respiratory distress syndrome (ARDS) is an acute respiratory failure characterized by progressive respiratory dyspnea and intractable hypoxemia caused by various causes both inside and outside the lungs. At present, there is still controversy about the monitoring of prone position（PP）ventilation in patients with severe hypoxemia. This article summarized a case of severe ARDS with type A H1N1 severe pneumonia treated with PP ventilation to improve oxygenation, so as to provide reference for clinical treatment.

Construction of a Transcriptome-Driven Network at the Early Stage of Infection with Influenza A H1N1 in Human Lung Alveolar Epithelial Cells

We aimed to understand the molecular changes in host cells that accompany infection by the seasonal influenza A H1N1 virus because the initial response rapidly changes owing to the fact that the virus has a robust initial propagation phase. Human epithelial alveolar A549 cells were infected and total RNA was extracted at 30 min, 1 h, 2 h, 4 h, 8 h, 24 h, and 48 h post infection (h.p.i.). The differentially expressed host genes were clustered into two distinct sets of genes as the infection progressed over time. The patterns of expression were significantly different at the early stages of infection. One of the responses showed roles similar to those associated with the enrichment gene sets to known ‘gp120 pathway in HIV.’ This gene set contains genes known to play roles in preventing the progress of apoptosis, which infected cells undergo as a response to viral infection. The other gene set showed enrichment of ‘Drug Metabolism Enzymes (DMEs).’ The identification of two distinct gene sets indicates that the virus regulates the cell's mechanisms to create a favorable environment for its stable replication and protection of gene metabolites within 8 h.

Oxigenação por membrana extracorpórea na síndrome do desconforto respiratório agudo devido à pneumonia por influenza A (H1N1) pdm09. Experiência em um único centro durante a temporada de 2013-2014 / Extracorporeal membrane oxygenation in acute respiratory distress syndrome due to influenza A (H1N1)pdm09 pneumonia. A single-center experience during the 2013-2014 season

RESUMO Objetivo: Descrever os desfechos de pacientes com síndrome do desconforto respiratório agudo associada à influenza subtipo H1N1 grave tratados com oxigenação por membrana extracorpórea. Métodos: Trata-se de revisão retrospectiva de uma coorte de pacientes oriunda de um único centro, constituída por adultos com síndrome do desconforto respiratório agudo relacionada com influenza subtipo H1N1 e tratados com oxigenação venovenosa por membrana extracorpórea durante a temporada de inverno no hemisfério norte de 2013/2014. Resultados: Dez pacientes receberam oxigenação venovenosa por membrana extracorpórea para tratamento de influenza subtipo H1N1 entre janeiro de 2013 e março de 2014. Sete deles foram transferidos para nosso centro visando à utilização de oxigenação por membrana extracorpórea dentro de um período de 72 horas após o início da ventilação mecânica. A idade mediana foi de 40 anos, sendo 30% dos pacientes do sexo feminino. O valor mediano da proporção entre pressão parcial de oxigênio e fração inspirada de oxigênio foi de 62,5, sendo o escore RESP mediano de 6. Três pacientes receberam inalação de óxido nítrico e quatro utilizaram posição prona como tratamento de resgate antes de ser iniciada a oxigenação por membrana extracorpórea. A duração mediana da ventilação mecânica foi de 22 dias (variação de 14 - 32). O tempo mediano de permanência na unidade de terapia intensiva foi de 27 dias (variação de 14 - 39). O tempo mediano de permanência no hospital foi de 29,1 dias (variação de 16,0 - 46,9). Ocorreram complicações não importantes de sangramento em seis dos dez pacientes. Oito dos dez pacientes sobreviveram até a alta hospitalar. Conclusão: Os sobreviventes eram relativamente jovens e tiveram alta com boas condições funcionais, o que salienta os anos de vida ajustados pela qualidade que foram salvos. Nossa experiência demonstra que mesmo um programa ainda relativamente novo de oxigenação por membrana extracorpórea pode desempenhar um papel importante, e proporcionar resultados excelentes para os pacientes mais graves.

ABSTRACT Objective: This report aimed to describe the outcomes of the patients with severe H1N1 associated acute respiratory distress syndrome who were treated with extracorporeal membrane oxygenation therapy. Methods: This retrospective review analyzed a single-center cohort of adult patients with H1N1-related acute respiratory distress syndrome who were managed with veno-venous extracorporeal membrane oxygenation during the winter of 2013/2014. Results: A total of 10 patients received veno-venous extracorporeal membrane oxygenation for H1N1 influenza between January 2013 and March 2014. Seven patients were transferred to our center for extracorporeal membrane oxygenation consideration (all within 72 hours of initiating mechanical ventilation). The median patient age was forty years, and 30% were female. The median arterial oxygen partial pressure to fraction of inspired oxygen ratio was 62.5, and the median RESP score was 6. Three patients received inhaled nitric oxide, and four patients were proned as rescue therapy before extracorporeal membrane oxygenation was initiated. The median duration of mechanical ventilation was twenty-two days (range, 14 - 32). The median length of stay in the intensive care unit was twenty-seven days (range, 14 - 39). The median hospital length of stay was 29.1 days (range, 16.0 - 46.9). Minor bleeding complications occurred in 6 of 10 patients. Eight of the ten patients survived to hospital discharge. Conclusion: The survivors were relatively young and discharged with good functional status (i.e., enhancing quality-adjusted life-years-saved). Our experience shows that even a relatively new extracorporeal membrane oxygenation program can play an important role in that capacity and provide excellent outcomes for the sickest patients.

Cambios en la presentación clínica de la influenza A H1N1pdm09 después de la pandemia / Changes in the clinical presentation of Influenza A H1N1pdm09 after the pandemic

Background: After the 2009 influenza pandemic the H1N1pdm09 strain circulate seasonally. In 2015, Puerto Montt Hospital in Chile faced a simultaneous outbreak of both seasonal H3N2 and H1N1pdm09 influenza A (IA). Aim: To evaluate the clinical differences between the two viral strains and recent changes in the behavior of H1N1pdm09 IA. Material and Methods: We set up a retrospective study including every adult hospitalized in Puerto Montt Hospital in 2015 due to IA, confirmed by reverse transcription polymerase chain reaction. We compared epidemiological data, clinical presentation, complications, and the outcome of patients with H1N1pdm09 versus those with seasonal influenza. In parallel, we compared 62 cases of thatH1N1 IA from 2015 with 100 cases who were hospitalized and analyzed in 2009. Results: Between July and October 2015, 119 adults with confirmed IA were hospitalized. From 2009 to 2015, the mean age of patients with IAH1N1pdm09 increased from 40.4 ± 17 to 58.8 ± 16 years (p < 0.01). Pneumonia as the cause of hospitalization decreased from 75 to 58% of patients, (p = 0.04). Likewise, the presence of comorbidities increased from 53 to 74%, (p < 0.01). Compared with seasonal H3N2, patients with IAH1N1pdm09 IA were more likely to require intensive care (p < 0.01) and mechanical ventilation (p < 0.01) and developed septic shock (p = 0.03). Their mortality was non-significantly higher (13 and 5% respectively). Conclusions: The clinical presentation of H1N1pdm09 IA has varied over time and now affects an older population, with a greater number of comorbidities. It also appears to be adopting the clinical behavior of a classic seasonal influenza virus.

Detección de virus influenza A, B y subtipos a (H1N1) pdm09, A (H3N2) por múltiple rt-pcr en muestras clínicas / Detection of influenza A, B and subtypes A (H1N1) pdm09, A (H3N2) viruses by multiple qrt-pcr in clinical samples

RESUMEN Objetivos. Estandarizar la técnica de reacción en cadena de la polimerasa en tiempo real (RT-PCR) múltiple para la detección de virus influenza A, B y tipificación de subtipos A (H1N1) pdm09, A (H3N2) en muestras clínicas. Materiales y métodos. Se analizaron 300 muestras de hisopado nasofaríngeo. Esta metodología fue estandarizada en dos pasos: la primera reacción detectó el gen de la matriz del virus de influenza A, gen de la nucleoproteína del virus influenza B y el gen GAPDH de las células huésped. La segunda reacción detectó el gen de la hemaglutinina de los subtipos A (H1N1) pandémico (pdm09) y A (H3N2). Resultados. Se identificaron 109 muestras positivas a influenza A y B, de las cuales 72 fueron positivas a influenza A (36 positivas a influenza A (H1N1) pdm09 y 36 positivos a influenza A (H3N2)) y 37 muestras positivas a influenza B. 191 fueron negativas a ambos virus mediante RT-PCR en tiempo real multiplex. Se encontró una sensibilidad y especificidad del 100% al analizar los resultados de ambas reacciones. El límite de detección viral fue del rango de 7 a 9 copias/µL por virus. Los resultados no mostraron ninguna reacción cruzada con otros virus tales como adenovirus, virus sincitial respiratorio, parainfluenza (1,2 y 3), metapneumovirus, subtipos A (H1N1) estacional, A (H5N2) y VIH. Conclusiones. La RT-PCR múltiple demostró ser una prueba muy sensible y específica para la detección de virus influenza A, B y subtipos A (H1N1, H3N2) y su uso puede ser conveniente en brotes estacionales.

ABSTRACT Objectives. To describe the clinical and epidemiological characteristics of patients diagnosed with epidermolysis bullosa (EB) at the Instituto Nacional de Salud (INSN) in Lima, Peru; a National Reference Center for this disease. Material and methods . Observational, descriptive and transversal study. We reviewed the clinical histories and laboratory tests of patients diagnosed with EB treated in INSN from 1993 to 2015. Results. 93 patients were registered. The average age was 7.9 ± 5.6 years; 53.8% (n = 50) were boys. Clinical forms corresponded to dystrophic EB with 41 (44.1%) cases, simple EB with 39 (41.9%) union EB cases with 8 (8.6%) and Kindler syndrome with 4 (4.3%) cases. The clinical form could not be identified in a case. A total of 48 cases (51.6%) came from Lima and Callao, and 45 cases (48.4%) from other provinces of the country. Extracutaneous manifestations involved gastrointestinal (44.1%), ocular (37.6%), odontogenic (87.1%), and nutritional (79.6%) involvement, as well as pseudosindactilia (16.1%). Chronic malnutrition (71.6%), acute malnutrition (17.6%) and anemia (62.4%) were found. Mortality corresponded to 6 cases (6.5%). Conclusions. 93 cases of EB were reported in INSN, the predominant clinical presentation was the dystrophic form.

Glomerulonefritis aguda con requerimiento de diálisis asociada a influenza A H1N1pdm09: comunicación de dos casos / Acute glomerulonephritis with hemodialysis requirement secondary to influenza A H1N1pdm09 infection: report of two cases

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.

La articulación público-privada en la producción de vacunas en México / Public-private articulation in the production of vaccines in Mexico

RESUMEN El artículo analiza el proceso de privatización de la atención a la salud: la Articulación Público-Privada (APP). Específicamente estudia la producción de vacunas em México, tomando como caso los Laboratorios de Biológicos y Reactivos de México, S.A. de C.V. (Birmex), empresa paraestatal, responsable de producir, distribuir e investigar biológicos y reactivos en México. Interesa destacar el comportamiento de Birmex durante el periodo de la pandemia de influenza de 2009, producida por el virus de la influenza A subtipo H1N1. Los resultados muestran que gracias al impulso de las políticas de liberalización y desregulación, existe una apertura de los servicios públicos a las corporaciones supranacionales.

ABSTRACT This paper analyzes the process of privatization of health care services through the Public-Private Articulation (APA). The production of vaccines in Mexico is studied, through the case study of Biological and Reagents Laboratories of Mexico, LLC (Birmex), company responsible for the production, distribution and investigation of biological and reagents in Mexico. It points out specially Birmex’s performance during the period of pandemic influenza A virus, H1N1 subtype. The results show that there exists opening of the public services to supranational corporations encouraged by policies of liberalization and deregulation.

Encefalopatía no fatal por influenza AH1N1 en paciente pediátrico / Non-fatal case of H1n1 influenza encephalopathy in a pediatric patient

RESUMEN Niña de dos años con fiebre y síntomas catarrales que presenta convulsiones focales de hemicuerpo derecho, las cuales persisten adicionándose signos de hipertensión endocraneana. Se identifica Influenza AH1N1 mediante reacción de cadena de polimerasa en hisopado nasofaríngeo. Paciente evoluciona favorablemente con medidas de soporte. No recibió Oseltamivir.

ABSTRACT A 2-year-old girl presented with fever, catarrhal symptoms, and focal right hemispheric seizures that persisted and led to signs of intracranial hypertension. An influenza A H1N1 infection was confirmed via polymerase chain reaction analysis of a nasopharyngeal swab. The patient, who was not treated with oseltamavir, has responded favorably to supportive measures.

Dimensiones políticas de una epidemia: el caso de la gripe A (H1N1) en la prensa escrita de Argentina / Political dimensions of an epidemic: the case of influenza A (H1N1) in the Argentine press / Dimensões políticas de uma epidemia: o caso da gripe A(H1N1) na imprensa escrita da Argentina

El objetivo de este estudio se orienta a comprender las representaciones sociales que expresan los periódicos, en torno a la epidemia de gripe A (H1N1) en Argentina para el año 2009, a través del análisis cuali-cuantitativo de dos dimensiones fundamentales: la forma en que se construye el "objeto" epidemia y las fuentes de información de las noticias. A partir de ello, es posible identificar que en la forma de nombrar y construir la epidemia subyace cierta decisión política de eliminar la responsabilidad que cabe a un modo de producción pecuaria riesgosa, responsabilizando al individuo que incurre en conductas de riesgo. El análisis muestra la vigencia de la hegemonía biomédica en las recomendaciones de representantes políticos, especialmente a nivel internacional, lo que contribuye a la farmacologización de una epidemia, posicionamiento que reproduce la población en sus reclamos. El comportamiento de la prensa ante la epidemia, no responde a eventos vinculados a la epidemiología del virus, sino que publica la mayor parte de noticias ante eventos asociados a la política local.

The current study addresses social representations of the influenza A (H1N1) epidemic in Argentina in 2009, in the country's mainstream newspapers. The methodology was twofold, qualitative and quantitative, with an analysis of two dimensions: the construction of the epidemic as an "object" (designation and characterization) and the sources of information in the news stories, seeking to identify the social actors involved in each case. The results show that designating the epidemic as "H1N1" rather than "swine flu" was a conscious political decision to exempt a hazardous form of livestock production from its role in the disease, while focusing responsibility on individual patients. The study addresses the relations between recommendations by policy spokespersons (especially at the international level), the pharmaceuticalization of the epidemic, shifting of the population's demands to validate biomedical hegemony, and local press coverage of the epidemic.

O presente estudo tem como objetivo compreender as representações sociais sobre a epidemia de influenza A (H1N1), na Argentina em 2009, nos jornais de maior circulação no país. A metodologia foi qualitativa e quantitativa com base na análise de duas dimensões: a forma em que se constrói o "objeto" epidemia (designação e caracterização dos mesmos) e as fontes de informação das notícias, procurando identificar em cada caso os atores sociais envolvidos. Os resultados mostram que na nomeação da epidemia fica a decisão política de eliminar a responsabilidade de um modo de produção de gado de risco, culpando o indivíduo. Observa-se que as recomendações dos representantes políticos, especialmente no nível internacional e promovida a farmacologização da epidemia, a reprodução do posicionamento da população em suas reivindicações que demonstra a validade da hegemonia biomédica e, finalmente, o comportamento da imprensa para a epidemia concentra-se em puramente ligado aos acontecimentos políticos locais.

¨Cómo informaron los medios de comunicación sobre la influenza AH1N1 en Perú? / How did the media report on the AH1N1 influenza in Perú?

Se analiza las características de las noticias emitidas por los medios de comunicación del Perú (MC) sobre influenza AH1N1 en el 2013, para lo cual se revisaron diariamente los MC escritos, radio, televisión e Internet. Las noticias se clasificaron según encuadre, valoración (educativa, informativa y con elevada percepción del riesgo de contagio y muerte -NEPRCM) y alcance. Se realizó un análisis descriptivo de las principales variables del estudio. El encuadre de la noticias estuvo centrado en los casos de influenza (47,5%) y las acciones del MINSA/otras instituciones (29,0%). El mayor porcentaje de noticias fueron de carácter informativo (73,7%), y solo el 7,5% fueron NEPRCM; estas últimas fueron más frecuentes en los diarios (9,0%) y televisión (9,4%). Durante el 2013, los MC, en general, fueron responsables al momento de informar, aunque hubo algunos que difundieron noticias que podrían haber incrementado la percepción de riesgo en la población.

We analyzed the characteristics of news issued by communication media (CM) in Peru on H1N1 influenza in 2013, for which written, radio, television and internet CM were reviewed daily. The news were classified according to framing, estimation (educational, informative and with high perception of risk of contagion and death) and scope. A descriptive analysis of the main variables of the study was made. The framing of the news was focused on influenza cases (47.5%) and actions of the Ministry of Health and other institutions (29.0%). The highest percentage of news was informative (73.7%), and only 7.5% were news with high perception of risk of contagion and death; the latter was more frequent in newspapers (9.0%) and television (9.4%). During 2013, the CM, in general, was responsible at the time of reporting, although there were some that spread news that could have increased the perception of risk in the population.

Cobertura vacinal contra influenza e motivos da não vacinação em crianças com idade de risco internadas em hospital terciário / Immunization against influenza and the reasons for non-immunization in children under age of risk hospitalized in tertiary hospital

Introdução: As crianças menores de 2 anos de idade apresentam importante fator de risco para internação e mortalidade por Influenza A H1N1. Morte é um desfecho incomum, mas seu risco é maior nesta faixa etária, especialmente, se há comorbidades associadas. As complicações incluem pneumonia viral e infecção bacteriana secundária. A principal intervenção preventiva é a imunização. O objetivo deste estudo foi descrever o percentual pediátrico imunizado, em duas campanhas consecutivas, verificar o motivo da não vacinação e comparar a frequência vacinal nos anos de 2012 e 2013. Métodos: Estudo de série histórica, abrangendo crianças internadas na faixa etária de risco - seis meses a dois anos. Foram feitos a revisão da caderneta vacinal e o inquérito aos responsáveis pelo paciente para identificar quem havia indicado a vacinação e qual o motivo da não vacinação. Resultados: Foram estudadas 191 crianças em 2012, e 226 em 2013, que se encontravam na faixa etária de risco. Em 2012, 71,2% dos pacientes foram vacinados e em 2013, 79,5% (P=0,05). A campanha foi o maior estímulo para a vacinação em 69% dos casos, e as principais causas da não vacinação foram gripe (31,4%) e desinformação (22,5%). Conclusão: Comparando os dois anos, verificou-se não haver diferença entre as coberturas vacinais, embora ainda permaneçam aquém do resultado registrado nacionalmente. A perda da campanha ainda está relacionada à gripe, neste período, fato que não é contraindicação. No entanto, ainda permanece um fator importante de impedimento, inclusive dos centros de referência em vacinação, como as Unidades Básicas de Saúde (AU)

Introduction: Children under 2 years of age present a significant risk factor for hospitalization and mortality from influenza A, H1N1. Death is an unusual outcome, but the risk is higher in this age group, especially if there are associated comorbidities. Complications include viral pneumonia and secondary bacterial infection. The main preventive intervention is immunization. The aim of this study was to describe the percentage of immunized children in two consecutive campaigns, check the reason for non-vaccination and compare the vaccination rate in years 2012 and 2013. Methods: Historical series study, including hospitalized children in the age group of risk, i.e., from six months to two years. Vaccination records were reviewed and a survey was carried out with parents/caregivers to identify who had indicated vaccination and the reason for non-vaccination. Results: 191 children were studied in 2012 and 226 in 2013, who were in the age group of risk. In 2012, 71.2% of patients were vaccinated and in 2013, 79.5% (P = 0.05). The campaign was the greatest stimulus for vaccination in 69% of cases, and the main causes of non-vaccination were influenza A (31.4%) and lack of information (22.5%). Conclusion: Comparing the two years, no difference in vaccination coverage was found, although the vaccination rates still remained below the nationally reported outcomes. During this period, missing the campaign was still related to the flu, a condition that is not a contraindication. However, it still remains an important factor of non-vaccination, even in the referral centers for vaccination, such as Basic Health Units (AU)

Fatores de risco para aquisição de influenza A (H1N1)pdm09 entre os profissionais de saúde / Risk factors for acquisition of influenza A (H1N1)pdm09 among health care workers

INTRODUÇÃO: Em junho de 2009 a Organização Mundial de Saúde declarou pandemia de influenza A (H1N1)pdm09. Esse novo vírus teve grande impacto na saúde mundial, foi responsável por 90% dos casos de influenza no mundo com apresentação clínica diferente da sazonal, acometendo indivíduos jovens e causando milhares de óbitos. O Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo foi referência para atendimento de casos graves. Por se tratar de um vírus novo houve controvérsias em relação a medidas de precaução e em relação ao afastamento dos profissionais de saúde (PAS). Devido a elevada incidência de influenza A (H1N1)pdm09 também ocorreram casos entre os profissionais da área da saúde (PAS). OBJETIVOS: Geral: Avaliar os fatores de risco para aquisição de influenza A (H1N1)pdm09 entre profissionais da área da saúde. Específico: Comparar características clínicas e de exposição dos casos de influenza A (H1N1)pdm09 em comparação a outros casos sintomáticos respiratórios entre profissionais da área da saúde MÉTODOS: Estudo caso-controle no qual foram criados três grupos e divididos em: sintomático respiratório H1N1-positivo, sintomático respiratório H1N1-negativo e controle assintomático. RESULTADOS: 274 PAS foram avaliados: 52 sintomáticos respiratórios H1N1-positivo, 120 sintomáticos respiratórios H1N1-negativo e 102 controles assintomáticos. Na análise multivariada que comparou sintomático respiratório H1N1-positivo com assintomáticos, presença de comorbidades/fatores de risco (OR=16,31; IC de 95%; 4,08-65,07) e contato desprotegido durante atendimento a caso suspeito e/ou confirmado para influenza A (H1N1)pdm09 em outro Hospital (OR=12,77; IC de 95%; 1,35-121,52) foram fatores de risco independentes para aquisição de influenza A (H1N1)pdm09. Contato social ou com colega de trabalho suspeito e/ou confirmado para influenza A (H1N1)pdm09 (OR=0,11; IC de 95%; 0,04-0,28) e uso de transporte público (OR=0,19; IC de 95%; 0,07-0,50)...

INTRODUCTION: In June 2009 the World Health Organization declared influenza A (H1N1) pdm09 pnademic. This new virus had great impact on global health and accounted for 90% of cases of influenza in the world. It affected young people and caused thousands of deaths. The Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo was a reference for the treatment of severe cases. Because it was a new virus there were controversies regarding the precautions and HCW sick leave policies. OBJECTIVE: General-To evaluate risk factors for acquisition of influenza A (H1N1) pdm09 among health care workers (HCW). Specific: To compare clinical and exposure characteristics of cases of influenza A (H1N1) pdm09 with other respiratory symptomatic infections among HCW. METHODS: Case-control study with three groups: symptomatic H1N1-positive cases, symptomatic H1N1-negative cases and asymptomatic controls. RESULTS: 274 HCW were evaluated: 52 symptomatic H1N1-positive cases, 120 symptomatic H1N1-negative cases and 102 asymptomatic controls. In the multivariate analysis that compared H1N1- symptomatic H1N1-positive cases with asymptomatic controls, comorbidities/risk factors (OR=16.31; 95% CI 4.08-65.07) and unprotected contact during caring for a confirmed or suspected case of influenza A (H1N1) pdm09 in another hospital (OR=12.77, 95% CI; 1.35- 121.52) were independent risk factors for pandemic influenza infection among HCW. Social contact or contact with co-worker with confirmed or suspected case of influenza A (H1N1) pdm09 (OR=0.11; 95% CI, 0.04- 0.28) and use of public transportation (OR= 0.19; 95% CI, 0.07- 0.50) were protective. Comparing symptomatics groups, unprotected contact during caring for a confirmed or suspected case of influenza A (H1N1) pdm09 in another hospital, to be a medical doctor, contact for or a confirmed or suspected case of influenza A (H1N1) pdm09 at home, reside with child from 5 to 12 years, fever and conjunctivitis were more common...