SARS-CoV-2 and influenza: a comparative overview and treatment implications / SARS-CoV-2 e influenza: revisión comparativa e implicaciones del tratamiento

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Alphainfluenzavirus are RNA viruses that cause coronavirus disease-19 and influenza, respectively. Both viruses infect the respiratory tract, show similar symptoms, and use surface proteins to infect the host. Influenza requires hemagglutinin and neuraminidase to infect, whereas SARS-CoV-2 uses protein S. Both viruses depend on a viral RNA polymerase to express their proteins, but only SARS-CoV-2 has a proofreading mechanism, which results in a low mutation rate compared to influenza. E1KC4 and camostat mesylate are potential inhibitors of SARS-CoV-2 S protein, achieving an effect similar to oseltamivir. Due to the SARS-CoV-2 low mutation rate, nucleoside analogs have been developed (such as EIDD-2801), which insert lethal mutations in the viral RNA. Furthermore, the SARS-CoV-2 low mutation rate suggests that a vaccine, as well as the immunity developed in recovered patients, could provide long-lasting protection compared to vaccines against influenza, which are rendered obsolete as the virus mutates.

Resumen La enfermedad por coronavirus de 2019 y la influenza son causadas por virus ARN: coronavirus tipo 2 del síndrome respiratorio agudo grave (SARS-CoV-2) y Alphainfluenzavirus, respectivamente. Ambos virus infectan el tracto respiratorio, presentan síntomas similares y emplean proteínas de superficie para infectar al huésped. El virus de la influenza requiere de hemaglutinina y neuraminidasa para infectar, mientras que el SARS-CoV-2 utiliza la proteína S. Ambos virus dependen de la ARN polimerasa viral para expresar sus proteínas, pero solo el SARS-CoV-2 cuenta con un mecanismo de corrección de errores, por lo que presenta una baja tasa de mutaciones en comparación con el virus de la influenza. E1KC4 y el mesilato de camostat son inhibidores potenciales de la proteína S del SARS-CoV-2, obteniendo un efecto similar al de oseltamivir. Aprovechando la baja tasa de mutación del SARS-CoV-2, se han desarrollado análogos de nucleósidos (como el fármaco EIDD-2801) que insertan mutaciones letales en el ARN viral. Además, la baja tasa de mutación del SARS-CoV-2, obteniendo un efecto similar al de oseltamivir sugiere que las vacunas desarrolladas, así como la inmunidad generada en pacientes recuperados, podrían brindar protección prolongada, en comparación con las vacunas desarrolladas contra la influenza, que resultan obsoletas frente a una cepa mutada.

Influenza A (H1N1): outbreak management in a dialysis unit and clinical outcomes of infection in chronic hemodialysis patients / Influenza A (H1N1): controle de surto em unidade de diálise e desfechos clínicos da infecção em pacientes em hemodiálise crônica

ABSTRACT Introduction: Chronic hemodialysis (HD) patients are considered to be at high risk for infection. Here, we describe the clinical outcomes of chronic HD patients with influenza A (H1N1) infection and the strategies adopted to control an outbreak of influenza A in a dialysis unit. Methods: Among a total of 62 chronic HD patients, H1N1 infection was identified in 12 (19.4%). Of the 32 staff members, four (12.5%) were found to be infected with the H1N1 virus. Outcomes included symptoms at presentation, comorbidities, occurrence of hypoxemia, hospital admission, and clinical evaluation. Infection was confirmed by real-time reverse transcriptase polymerase chain reaction. Results: The 12 patients who had H1N1 infection did not differ significantly from the other 50 non-infected patients with respect to age, sex, dialysis vintage, dialysis modality, or proportion of comorbidities. Obesity was higher in the H1N1-infected group (41.5 vs. 4%, p<0.002). The most common symptoms were fever (92%), cough (92%), and rhinorrhea (83%). Early empirical antiviral treatment with oseltamivir was started in symptomatic patients and infection control measures, including the intensification of contact-reduction measures by the staff members, antiviral chemoprophylaxis to asymptomatic patients undergoing HD in the same shift of infected patients, and dismiss of staff members suspected of being infected, were implemented to control the spread of infection in the dialysis unit. Conclusion: The clinical course of infection with H1N1 in our patients was favorable. None of the patients developed severe disease and the strategies adopted to control the outbreak were successful.

RESUMO Introdução: Pacientes em hemodiálise (HD) crônica apresentam risco elevado para infecções. O presente estudo descreve os desfechos clínicos de pacientes em HD crônica com infecção pelo vírus influenza A (H1N1) e as estratégias adotadas para controlar um surto de influenza A numa unidade de diálise. Métodos: Doze (19,4%) de 62 pacientes em HD crônica e quatro (12,5%) de 32 funcionários desta unidade de diálise apresentaram infecção pelo vírus H1N1. Os desfechos incluíram sintomas à apresentação, comorbidades, ocorrência de hipoxemia, internação hospitalar e avaliação clínica. A presença de infecção foi confirmada por reação em cadeia da polimerase via transcriptase reversa (RT-PCR) em tempo real. Resultados: Os 12 pacientes com infecção por H1N1 não diferiram significativamente dos 50 pacientes sem infecção no tocante a idade, sexo, tempo em diálise, modalidade de diálise e percentual de comorbidades. O percentual de obesidade foi mais elevado no grupo com infecção por H1N1 (41,5% vs. 4%, p<0,002). Os sintomas mais comuns foram febre (92%), tosse (92%) e rinorreia (83%). Os pacientes foram submetidos a tratamento antiviral com oseltamivir e medidas de controle (intensificação das medidas de redução de contato pelos funcionários da clínica, quimioprofilaxia com antiviral para pacientes assintomáticos em HD na mesma sala dos pacientes com infecção e afastamento de funcionários da clínica com suspeita de infecção) para controlar a disseminação da infecção pela unidade de diálise. Conclusão: O curso clínico da infecção por H1N1 em nossos pacientes foi favorável. Nenhum evoluiu para doença grave e as estratégias adotadas foram efetivas no controle do surto.

Influenza A and B in a cohort of outpatient children and adolescent with influenza like-illness during two consecutive influenza seasons

ABSTRACT Introduction Influenza is an important cause of morbimortality worldwide. Although people at the extremes of age have a greater risk of complications, influenza has been more frequently investigated in the elderly than in children, and inpatients than outpatients. Yearly vaccination with trivalent or quadrivalent vaccines is the main strategy to control influenza. Objectives Determine the clinical and molecular characteristics of influenza A and B infections in children and adolescents with influenza-like illness (ILI). Methods: A cohort of outpatient children and adolescents with ILI was followed for 20 months. Influenza was diagnosed with commercial multiplex PCR platforms. Results: 179 patients had 277 episodes of ILI, being 79 episodes of influenza A and 20 episodes of influenza B. Influenza A and B cases were mild and had similar presentation. Phylogenetic tree of influenza B viruses showed that 91.6% belonged to the B/Yamagata lineage, which is not included in trivalent vaccines. Conclusions: Influenza A and B are often detected in children and adolescents with ILI episodes, with similar and mild presentation in outpatients. The mismatch between the circulating influenza viruses and the trivalent vaccine offered in Brazil may have contributed to the high frequency of influenza A and B in this population.

Influenza A(H1N1)pdm09 infection and viral load analysis in patients with different clinical presentations

BACKGROUND Influenza viral load (VL) can be a decisive factor in determining the antiviral efficacy in viral clearance. OBJECTIVE This study aimed to evaluate the rate of infection and the role of influenza VL on the clinical spectrum of illnesses among different patient groups attended at a tertiary hospital in Brazil. METHODS Samples were collected from patients presenting acute respiratory infection from 2009 to 2013. Overall, 2262 samples were analysed and distributed into three groups: (i) asymptomatic (AS); (ii) symptomatic outpatients (OP); and (iii) hospitalised patients (HP). VL (expressed in Log10 RNA copies/mL) was calculated through a quantitative real-time one-step reverse transcription-polymerase chain reaction (RT-PCR) assay aimed at the M gene, with human RNAseP target as internal control and normalising gene of threshold cycle values. FINDINGS A total of 162 (7.16%) H1N1pdm09 positive samples were analysed. Patients aged from 0.08 to 77 years old [median ± standard deviation (SD): 12.5 ± 20.54]. Children with 5 to 11 years old presented the highest detection (p < 0.0001). AS patients had the lowest VL, with a significant difference when compared with symptomatic patients (p = 0.0003). A higher VL was observed within two days of disease onset. Ten patients (HP group) received antiviral treatment and were followed up and presented a mean initial VL of 6.64 ± 1.82. A complete viral clearance for 50% of these patients was reached after 12 days of treatment. MAIN CONCLUSIONS It is important to evaluate AS patients as potential spreaders, as viral shedding was still present, even at lower VL. Our results suggest that patients with underlying diseases and severe clinical symptoms may be considered for prolonged viral treatment.

Clinical-epidemiological profile of deaths from influenza with a history of timely vaccination, Mexico 2010-2018

Introduction: Influenza epidemics are of higher risk at the extremes of life and in people with comorbidities. Effective vaccination prevents the occurrence of serious cases and decreases mortality. Objective: To describe deaths from influenza with a history of timely vaccination, from the 2010 to the 2018 season in Mexico. Method: Cross-sectional, descriptive study where the Influenza Epidemiological Surveillance System database was used. Results: From 2010 to 2018, 65 vaccinated individuals died from influenza, from which 55% of cases (n = 36) were due to type A (H1N1), 51% (n = 33) were females, median age was 57 years, 21 % (n = 14) did not meet the operational definition of influenza-like illness or severe acute respiratory infection, 83% (n = 54) had at least one comorbidity, with the most common being diabetes mellitus and hypertension (32% each); 55% (n = 36) of deaths received antiviral treatment and only 8% (n = 5) had no comorbidities and received treatment with oseltamivir. Conclusions: Deaths from influenza with timely vaccination represent a very low percentage of the totality. Vaccination against influenza has been a specific prevention strategy that decreases disease burden.

Parotiditis e influenza: inusual asociación durante 2017, en Santa Fe, Argentina / Parotitis and influenza: unusual association during 2017, in Santa Fe, Argentina

Resumen Introducción: La parotiditis es una enfermedad vírica aguda caracterizada por tumefacción y dolor en una o ambas glándulas salivales, submaxilar o submentoniana, fiebre, dolor de cabeza, dolor muscular y/o fatiga. Objetivos Investigar la ocurrencia de infección por el virus influenza en casos de parotiditis en una población de Santa Fe, durante 2017 y analizar las características clínicas y epidemiológicas de los casos. Materiales y Métodos: Se estudiaron pacientes con diagnóstico de parotiditis, que acudieron a la consulta desde la semana 26 en la red de médicos que forman la Unidad Centinela de Influenza en Santa Fe. Resultados: Entre las semanas epidemiológicas 26 y 44, se incluyeron 22 casos de parotiditis clínica. El virus influenza se detectó en 68,2%, influenza A (H3N2) 93% e influenza B 7%. Los síntomas clínicos de los casos fueron leves, con una tumefacción de cinco días y sin complicaciones. El 74% presentó una enfermedad tipo influenza en conjunto con la parotiditis. Conclusiones: Este estudio evidencia que niños que presentaban parotiditis tenían una infección por el virus de la influenza A (H3N2). Es necesario implementar una vigilancia sistemática de las parotiditis asociadas con influenza y el diagnóstico diferencial, incluso en ausencia de síntomas respiratorios.

Background: Parotitis is an acute viral disease characterized by swelling and pain in one or both salivary glands, submaxillary or submental, fever, headache, muscle ache and/or fatigue. Aim: To investigate the occurrence of influenza virus infection in parotitis cases in a population of Santa Fe during 2017 and analyze clinical and epidemiological characteristics of the cases. Methods: We studied patients with diagnosis of mumps without age restriction, who came for examination from week 26 to the network of clinicians forming the Sentinel Influenza Unit in Santa Fe. Results: Between epidemiological weeks 26 and 44, 22 clinical parotitis cases we enrolled. The influenza virus was detected in 68.2%, influenza A (H3N2) 93%, and influenza B, 7%. The clinical signs of cases were mild, with an average swelling development of 5 days and no complications. 74% presented with influenza-like illness in tandem with parotitis. Conclusions: This study provides evidence that a proportion of children presenting with parotitis had influenza A(H3N2) virus infection. It is necessary to implement systematic surveillance of parotitis associated with influenza and differential diagnosis even in the absence of respiratory symptoms.

Miocarditis fulminante en adultos por el virus de la influenza B: reporte de dos casos y revisión de la literatura / Fulminant myocarditis due to the influenza B virus in adults: Report of two cases and literature review

Resumen La miocarditis es una enfermedad inflamatoria del miocardio. Las infecciones virales son la causa más común, aunque también puede deberse a reacciones de hipersensibilidad y de etiología autoinmunitaria, entre otras. El espectro clínico de la enfermedad es variado y comprende desde un curso asintomático, seguido de dolor torácico, arritmias y falla cardiaca aguda, hasta un cuadro fulminante. El término 'fulminante' se refiere al desarrollo de un shock cardiogénico con necesidad de soporte vasopresor e inotrópico o dispositivos de asistencia circulatoria, ya sea oxigenación por membrana extracorpórea o balón de contrapulsación intraaórtico. Cerca del 10 % de los casos de falla cardiaca por miocarditis corresponde a miocarditis fulminante. La miocarditis por influenza se considera una condición infrecuente; no obstante, su incidencia ha aumentado desde el 2009 a raíz de la pandemia de influenza por el virus AH1N1. Por su parte, la miocarditis por influenza de tipo B sigue siendo una condición infrecuente. Se describen aquí dos casos confirmados de miocarditis fulminante por el virus de la influenza B atendidos en un centro cardiovascular, que requirieron dispositivos de asistencia circulatoria mecánica.

Abstract Myocarditis is an inflammatory disease of the myocardium. Viral infections are the most common cause, although it can also be due to hypersensitivity reactions and autoimmune etiology, among other causes. The clinical spectrum of the disease is varied, from an asymptomatic course, followed by chest pain, arrhythmias, and acute heart failure, to a fulminant episode. The term fulminant refers to the development of cardiogenic shock with a need for vasopressor support and inotropic or assisted circulation devices either extracorporeal membrane oxygenation (ECMO) or intra-aortic counterpulsation balloon. About 10% of cases of heart failure due to myocarditis correspond to fulminant myocarditis. Influenza myocarditis has been considered an infrequent condition. However, its incidence has increased since 2009 as a result of the AH1N1 pandemic; otherwise, myocarditis due to the Influenza type B virus remains an infrequent entity. We describe the experience in a cardiovascular center of two confirmed cases of fulminant myocarditis due to influenza B that required circulatory assistance devices.

Encefalitis por virus influenza B en un paciente adulto: reporte de caso / Encephalitis caused by type B influenza virus in an adult: report of one case

Neurological manifestations associated with influenza virus infection include encephalitis, encephalopathy, acute necrotizing encephalitis, transverse myelitis, acute disseminated encephalomyelitis, mild encephalitis with reversible splenial syndrome (MERS), and Guillaín Barré syndrome. We report a 16-year-old female who was admitted at our emergency department with seizures, confusion, nystagmus and motor clumsiness five days after an upper a respiratory tract infection. Influenza type B virus infection was confirmed by chain polymerase reaction analysis. The initial electroencephalogram demonstrated a pattern of global slowness without epileptic discharges. One week later, it showed a progression to slow-wave focal bilateral discharges at both temporal and occipital lobes. The patient had a favorable evolution and was discharged 19 days after admission with phenytoin to prevent seizures.

Viral detection profile in children with severe acute respiratory infection

ABSTRACT Objectives: The role of viral co-detection in children with severe acute respiratory infection is not clear. We described the viral detection profile and its association with clinical characteristics in children admitted to the Pediatric Intensive Care Unit (PICU) during the 2009 influenza A(H1N1) pandemic. Method: Longitudinal observational retrospective study, with patients aged 0-18 years, admitted to 11 PICUs in Rio de Janeiro, with suspected H1N1 infection, from June to November, 2009. The results of respiratory samples which were sent to the Laboratory of Fiocruz/RJ and clinical data extracted from specific forms were analyzed. Results: Of 71 samples, 38% tested positive for H1N1 virus. Of the 63 samples tested for other viruses, 58 were positive: influenza H1N1 (43.1% of positive samples), rhinovirus/enterovirus (41.4%), respiratory syncytial vírus (12.1%), human metapneumovirus (12.1%), adenovirus (6.9%), and bocavirus (3.5%). Viral codetection occured in 22.4% of the cases. H1N1-positive patients were of a higher median age, had higher frequency of fever, cough and tachypnea, and decreased leukometry when compared to H1N1-negative patients. There was no difference in relation to severity outcomes (number of organic dysfunctions, use of mechanical ventilation or amines, hospital/PICU length of stay or death). Comparing the groups with mono-detection and co-dection of any virus, no difference was found regarding the association with any clinical variable. Conclusions: Other viruses can be implicated in SARI in children. The role of viral codetection has not yet been completely elucidated.

The influenza season 2016/17 in Bucharest, Romania - surveillance data and clinical characteristics of patients with influenza-like illness admitted to a tertiary infectious diseases hospital

ABSTRACT Background: Influenza continues to drive seasonal morbidity, particularly in settings with low vaccine coverage. Objectives: To describe the influenza cases and viral circulation among hospitalized patients. Methods: A prospective study based on active surveillance of inpatients with influenza-like illness from a tertiary hospital in Bucharest, Romania, in the season 2016/17. Results: A total of 446 patients were tested, with a balanced gender distribution. Overall, 192 (43%) patients tested positive for influenza, with the highest positivity rate in the age groups 3-13 years and >65 years. Peak activity occurred between weeks 1 and 16/2017, with biphasic distribution: A viruses were replaced by B viruses from week 9/2017; B viruses predominated (66.1%). Among the 133 (69.3%) subtyped samples, all influenza A were subtype H3 (n = 57) and all influenza B were B/Victoria (n = 76). Patients who tested positive for influenza presented fewer comorbidities (p = 0.012), except for the elderly, in whom influenza was more common in patients with comorbidities (p = 0.050). Disease evolution was generally favorable under antiviral treatment. The length of hospital stay was slightly longer in patients with influenza-like illness who tested patients negative for influenza (p = 0.031). Conclusions: Distinctive co-circulation of A/H3 and B/Victoria in Bucharest, Romania in the 2016/17 influenza season was found. While the A/H3 subtype was predominant throughout Europe that season, B/Victoria appears to have circulated specifically in Romania and the Eastern European region, predominantly affecting preschoolers and school children.

Adultos con influenza, evolución clínica, costos y grupos relacionados por el diagnóstico, resultados de 4 años. Clínica Dávila. Santiago de Chile / Adults patients with influenza, clinical evolution, cost and diagnosis related groups, four years results. Clinica Dávila, Santiago, Chile

Resumen Introducción: En 2009 la Influenza A H1N1pdm09 provocó en Chile 12.258 casos y 155 muertes. Objetivo: Analizar en adultos egresados de Clínica Dávila con influenza, en 2009, 2010, 2012 y 2014, soporte ventilatorio, costo de hospitalización, Grupos Relacionados por el Diagnóstico (GRD) y letalidad. Material y Método: Estudio descriptivo retrospectivo usando la ficha médica electrónica. Resultados: Egresaron 115.673 adultos, 338 (0,29%) con diagnóstico de Influenza, edad 56,5 ± 22 años, 59% mujeres, letalidad 4%. Hubo 3 grupos, Grupo 1: sin ningún soporte ventilatorio, 295 pacientes, edad 63 ± 20, estadía 6,6 ± 6,9 días, costo promedio de hospitalización $2.885.261, mediana peso GRD 0,41 (p25 = 0,38 y p75 = 0,62), letalidad 1,01% (3 pacientes). Grupo 2: Ventilación mecánica no invasiva (VMNI), 23 casos, edad 77,1 ± 13, letalidad 22% (5 casos), estadía 16,8 ± 12,4, costo $9.245.242, GRD 0,79 (p25 = 0,62 y p75=1,03). Grupo 3: Intubación y ventilación mecánica invasiva (VMI), 20 pacientes, edad 56,4 ± 15, estadía 36,9 ± 41,4, costo $38.681.099, GRD 5,86 (p25 = 5,82 y p75 = 5,86) y letalidad 30% (6 pacientes). Los GRD grupo VMI versus grupo VMNI y ningún soporte fueron diferentes (p < 0,0001 y p < 0,0001 respectivamente). La letalidad por influenza el 2014 fue de 8,5%, mientras que en los años 2012, 2010 y 2009 fue 1,5%, 3% y 2,5% respectivamente. La mediana de edad el año 2009 fue 37,5 años, menor que la de los otros años (p < 0,0001). Conclusiones: En 2009 los pacientes fueron más jóvenes, la necesidad de soporte ventilatorio provocó un peso GRD, estadía, costo y letalidad mayores que aquellos que no lo requirieron.

Introduction: In 2009 Influenza A H1N1pdm09 caused in Chile 12,258 cases and 155 deaths. Objective: To analyze ventilatory support, cost of hospitalization, Diagnosis Related Groups (DRG) and lethality in adults patients with influenza discharged from our institution, during 2009, 2010, 2012 and 2014. Patients and Method: Retrospective descriptive study using electronic medical records. Results: 115,673 adults were discharged, 338 (0.29%) with diagnosis of Influenza, age 56.5 ± 22 yr.o., 59% women, lethality 4%. There were 3 groups, Group 1: without any ventilatory support, 295 patients, age 63 ± 20, stay 6.6 ± 6.9 days, average cost of hospitalization 2,885,261 clp, medium weight DRG 0.41 (p25 = 0.38) andp75 = 0.62), lethality 1.01% (3 patients). Group 2: Non-invasive mechanical ventilation (NIMV), 23 cases, age 77.1 ± 13, lethality 22% (5 cases), stay 16.8 ± 12.4, cost 9,245,242 clp, DRG 0.79 (p25 = 0.62 and p75 = 1.03). Group 3: Intubation and invasive mechanical ventilation (IMV), 20 patients, age 56.4 ± 15, stay 36.9 ± 41.4, cost 38.681.099 clp, DRG 5.86 (p25 = 5.82 and p75 = 5,86) and lethality 30% (6 patients). The DRG group VMI versus group VMNI and no support were different (p < 0.0001 and p < 0.0001 respectively). The lethality for influenza in 2014 was 8.5%, while in 2012, 2010 and 2009 it was 1.5%, 3% and 2.5% respectively. The median age in 2009 was 37.5 yr.o significantly minor, than the other years (p < 0.0001). Conclusions: In 2009 the patients were younger, the need for ventilatory support led to a higher DRG weight, stay, cost and lethality than those who did not require it.

A cien años de la gripe "española / One hundred years after the "Spanish" flu

La pandemia de gripe "española", de la que se cumplen 100 años, es considerada la más devastadora de la historia. Se estima que afectó a un tercio de la población mundial, y más del 2.5% de los enfermos murieron. Esta pandemia se presentó en dos oleadas principales, en 1918 y 1919, y la morbimortalidad por edades tuvo una curva en W. En general, la muerte no ocurría como consecuencia directa de la gripe, sino por bronconeumonías bacterianas, para las que se carecía de tratamiento. Hubo, además, una mayor mortalidad en enfermos con tuberculosis preexistente con respecto al resto de los afectados de influenza. En Argentina la epidemia también se presentó en dos oleadas principales, con amplias variaciones en la mortalidad por regiones. El tratamiento disponible incluía dieta, antisepsia de garganta, valerianato de quinina, salicilato, codeína para la tos y aceite alcanforado. También se aplicaban primitivas vacunas y sueros anti-neumococos. Con la disponibilidad de la secuencia de ARN completa del genoma del virus de la influenza 1918 ha sido posible ensamblar, mediante genética inversa, partículas virales semejantes a las de la pandemia mortal. El virus reconstituido demostró ser extraordinariamente virulento para ratones. En la actualidad, la vacunación contra la gripe estacional reduce el riesgo de otra pandemia, pero por el momento no puede eliminarlo. El desarrollo de vacunas "universales" contra la gripe, que confieran inmunidad confiable y duradera, podrá evitar en el futuro su propagación mundial.

The "Spanish" flu pandemic, which occurred a century ago, is considered the most devastating in human history. An estimated one third of world population fell ill with flu and more than 2.5% of them died. The course of the epidemic had two main waves (1918 and 1919) and showed an unusual W-shaped morbidity/mortality distribution. Death was not a direct outcome of flu itself but rather a consequence of secondary bacterial bronchopneumonia, for which antibiotics had not yet been discovered. Pre-existing pulmonary tuberculosis was also accountable for increased flu death rates during the pandemic. As it happened in Europe, in Argentina the epidemic had two main waves, with ample variation in mortality by region. Available treatment at the time included diet, throat antiseptic rinses, low doses of quinine valerianate, salicylates, codeine as a cough suppressant, and camphor oil. Primitive anti-pneumococcal vaccines and immune sera were also applied. Upon the disclosure of the whole RNA sequence of the 1918 influenza virus genome, by means of reverse genetics it was possible to assemble viral particles resembling those of the deadly pandemic. The reconstituted virus proved to be extraordinarily virulent for mice. Current seasonal flu vaccines help to reduce, but not to abolish, the risk of another pandemic. The ongoing development of "universal" vaccines against influenza conferring reliable and long-lasting immunity may prevent its global spread in the future.

Influenza A não H1N1 associada à insuficiência respiratória e à insuficiência renal aguda em paciente com fibrose cística previamente vacinado / Influenza A non-H1N1 associated with acute respiratory failure and acute renal failure in a previously vaccinated cystic fibrosis patient

RESUMO No período sazonal compreendido entre 2014 e 2015, a maior parte das infecções por influenza decorreu do vírus influenza A H3N2. Mais de dois terços dos vírus influenza A H3N2 circulante eram antigênica e geneticamente diferentes (drift) do componente A H3N2 da vacina da influenza sazonal 2014 - 2015 para os hemisférios norte e sul. O objetivo deste trabalho foi relatar um caso de infecção por influenza A sazonal não H1N1 ocorrido em junho de 2015 em um paciente adulto com fibrose cística com doença pulmonar grave, previamente vacinado com a vacina antigripal trivalente. O paciente evoluiu com insuficiências respiratória e renal (sem rabdomiólise), sendo submetido à ventilação mecânica e à hemodiálise. A evolução clínica foi positiva após 39 dias de permanência hospitalar. Ainda, o paciente permaneceu clinicamente estável após seguimento de 18 meses. Com os avanços recentes na medicina intensiva e no tratamento, a sobrevivência com uma doença pulmonar avançada na fibrose cística apresenta novas questões e problemas potenciais, que ainda estão sendo formulados.

ABSTRACT In the 2014 - 2015 season, most influenza infections were due to A (H3N2) viruses. More than two-thirds of circulating A (H3N2) viruses are antigenically and genetically different (drifted) from the A (H3N2) vaccine component of 2014 - 2015 northern and southern Hemisphere seasonal influenza vaccines. The purpose of this paper is to report a case of seasonal influenza A non-H1N1 infection that occurred in June 2015 in an adult cystic fibrosis patient with severe lung disease previously vaccinated with the anti-flu trivalent vaccine. The patient evolved to respiratory and renal failure (without rhabdomyolysis) and was placed under mechanical ventilation and hemodialysis. The clinical outcome was positive after 39 days of hospital stay. In addition, the patient was clinically stable after 18 months of follow-up. With the recent advances in critical care medicine and in cystic fibrosis treatment, survival with advanced pulmonary disease in cystic fibrosis presents new questions and potential problems, which are still being formulated.

Epidemiology of human infection with avian influenza A(H7N9) virus in China, 2013-2017 / 中华流行病学杂志

Objective: To understand the epidemiological characteristics of human infection with avian influenza A (H7N9) virus in China, and provide evidence for the prevention and control of human infection with H7N9 virus. Methods: The published incidence data of human infection with H7N9 virus in China from March 2013 to April 2017 were collected. Excel 2007 software was used to perform the analysis. The characteristics of distribution of the disease, exposure history, cluster of the disease were described. Results: By the end of April 2017, a total of 1 416 cases of human infection with H7N9 virus were confirmed in China, including 559 deaths, the case fatality rate was 39.5%. In 2016, the case number was lowest (127 cases), with the highest fatality rate (57.5%). The first three provinces with high case numbers were Zhejiang, Guangdong and Jiangsu. The median age of the cases was 55 years and the male to female ratio was 2.3∶1. Up to 66% of cases had clear live poultry exposure history before illness onset, 31% of cases had unknown exposure history and only 3% of the cases had no live poultry exposure history. There were 35 household clusters (5 in 2013, 9 in 2014, 6 in 2015, 5 in 2016, 10 in 2017), which involved 72 cases, accounting for 5% of the total cases. Conclusions: The epidemic of human infection with H7N9 virus in China during 2013-2017 had obvious seasonality and spatial distribution. There was limited family clustering. Infection cases were mostly related to poultry contact.

A case of human infection with highly pathogenic avian influenza A (H7N9) virus through poultry processing without protection measure / 中华流行病学杂志

Objective: To investigate the infection pattern and etiological characteristics of a case of human infection with highly pathogenic avian influenza A (H7N9) virus and provide evidence for the prevention and control of human infection with highly pathogenic avian influenza virus. Methods: Epidemiological investigation was conducted to explore the case's exposure history, infection route and disease progression. Samples collected from the patient, environments and poultry were tested by using real time reverse transcriptase-polymerase chain reaction (RT-PCR). Virus isolation, genome sequencing and phylogenetic analysis were conducted for positive samples. Results: The case had no live poultry contact history, but had a history of pulled chicken processing without taking protection measure in an unventilated kitchen before the onset. Samples collected from the patient's lower respiratory tract, the remaining frozen chicken meat and the live poultry market were all influenza A (H7N9) virus positive. The isolated viruses from these positive samples were highly homogenous. An insertion which lead to the addition of multiple basic amino acid residues (PEVPKRKRTAR/GL) was found at the HA cleavage site, suggesting that this virus might be highly pathogenic. Conclusions: Live poultry processing without protection measure is an important infection mode of "poultry to human" transmission of avian influenza viruses. Due to the limitation of protection measures in live poultry markets in Guangzhou, it is necessary to promote the standardized large scale poultry farming, the complete restriction of live poultry sales and centralized poultry slaughtering as well as ice fresh sale.

A review on the preparedness plans on influenza pandemics, by WHO and China: the current status and development / 中华流行病学杂志

Every influenza pandemic in history would end up with disastrous outcomes on mankind, of which the most notorious one was the "Spanish flu" pandemic in 1918. In the past century, with advanced knowledge on influenza viruses, laboratory technologies and surveillance methods, human beings were not as helpless when facing the influenza pandemic. In order to control the outbreaks and reducing the negative impacts, programs as: setting up and improving the influenza pandemic preparedness and response plan were recognized as important issues on early detection or prompt warning of any influenza virus strain that might lead to potential pandemics. The scheduled and planned control measures towards the pandemic preparedness and response plan had been considered of key importance in mitigating the peak of pandemic or controlling the transmission of virus. Since the "1918 influenza pandemic" , we had reviewed the evolution and development of plans regarding the preparedness and response on influenza pandemic issued by both WHO and China. We also emphasized on the variety of strategies which were linked to the preparedness and response at different historical stages, to provide reference for the pandemic preparedness of the disease, in the future.

Development and prospect of Influenza Surveillance Network in China / 中华流行病学杂志

The annual seasonal epidemic of influenza caused serious disease burden around the world, and serious social panic and economic losses. Due to the high variability and uncertainty of influenza virus, prevention and control of influenza faces many challenges. Surveillance is a key strategy to prevent and control influenza, and influenza is the first infectious disease to be monitored globally. More than 60 years, influenza surveillance programs in China has made great contributions to the prevention and control of influenza in China and the world. Especially in the past 10 years, the influenza surveillance network has developed rapidly, the scale has been expanded significantly, the monitoring content and scope have been continuously improved, and the monitoring quality has been rapidly improved. The China Influenza Surveillance Network is one of the early detection systems for emerging infectious diseases in China and the world. It helps to improve the capacity of public health system in prevention and control and early warning of emerging infectious diseases.

Epidemiological characteristics of influenza in Guangdong province, during winter of 2017-2018 / 中华流行病学杂志

Objective: To understand the epidemiological characteristics of influenza in Guangdong province, during the winter of 2017-2018, to provide evidence for response to the diversity of influenza, in different seasonal patterns. Methods: Data on weekly influenza surveillance from January 2016 to April 2018, were collected in Guangdong. Information on patients with Influenza-like illness (ILI), on influenza virus positive rates and on outbreaks during the winter of 2017 to 2018, was analyzed and compared with those in spring of 2016 and summer of 2017. χ(2) test and Fisher exact test were used. Results: In the above said winter, the average percentage of visits for ILI in 28 hospitals where sentinel surveillance program had been set, was 4.99% (157 235/3 149 656), which was above the level of the same period in the previous five years. The positive rates of influenza virus among samples collected from ILI outpatients and hospitalized cases under severe acute respiratory infection (SARI) were 28.33% (2 137/7 543) and 14.93% (256/1 715), with the proportions of B (Yamagata) as 70.43% (1 505/2 137) and 73.05% (187/256) respectively. A total of 257 influenza outbreaks were reported in the winter period, with 82.49% (212/257) occurred in elementary schools. Cases aged 6-14 years occurred in winter and spring appeared of having higher positive rate than those seen in summer (P<0.05) whereas elderly cases aged 60 and above showed higher positive rate in summer than those in winter and spring two seasons (P<0.05). Conclusions: Epidemiological characteristics of influenza appeared in Guangdong province, during the winter from 2017 to 2018, were correlated to Influenza B (Yamagata). Capacity on the implementation of surveillance programs and on the coverage of vaccination should be improved and increased in order to control influenza in different epidemic seasons, in Guangzhou.

The influence of statutory holidays on the proportion of the outpatient and emergency visits for influenza-like illness / 中华流行病学杂志

Objective: To analyze the reasons for the fluctuations in the percentage of outpatient or emergency visits for influenza-like illness (ILI) during the Spring Festival and National Day in 2014-2018 surveillance season. Methods: ILI surveillance data was collected during the period of Spring Festival and National Day in mainland China, and downloaded from Chinese Influenza Surveillance Information System, during the 2014-2018 surveillance season. Results: There was no significant difference noticed in the number of ILI reports in the festival week with weeks before or after in both the southern and northern provinces. The number of outpatient visits was much less than that of the week before and after, but the number of emergency visits was statistically significantly increased. Conclusion: In the holiday peak of ILI%, the major causes was the impact of holiday-off at sentinel hospitals, resulting in a large reduction in the number of outpatient visits in the consulting room during the festivals.