Efficacy of oseltamivir compared with zanamivir in COPD patients with seasonal influenza virus infection: a randomized controlled trial

Influenza viruses exacerbate chronic obstructive pulmonary disease (COPD) with considerable morbidity and mortality. Zanamivir and oseltamivir are effective in treating influenza. However, their efficacy in relieving influenza symptoms in COPD patients remains unknown, with the lack of controlled trials in this subject. Therefore, we conducted this randomized controlled trial to investigate the clinical efficacy of both interventions in this population. Patients were allocated to two groups (80 patients each): oseltamivir (OSELTA) and zanamivir (ZANA) groups. Oseltamivir (75 mg) was orally administered twice daily for 5 days, while zanamivir (10 mg) was inhaled twice daily for 5 days. Clinical parameters including body temperature, influenza symptoms (i.e., sore throat, cough, etc.), and serial blood tests were recorded on days 1, 3, and 7. We analyzed primary (changes in body temperature) and secondary outcomes (changes in non-specific symptoms) using the pre-protocol and intention-to-treat analyses. Differences between groups were assessed using t-test. Oseltamivir and zanamivir significantly reduced body temperature on the 3rd day after treatment; however, the number of patients who reported clinical improvement in influenza-like symptoms was significantly higher in the OSELTA group compared to the ZANA group on days 3 (85 vs 68.8%, P=0.015) and 7 (97.5 vs 83.8%, P=0.003). However, no significant changes in hematological (white blood cells and its subtypes) and inflammatory (C-reactive protein) parameters were noted (P>0.05). Our results suggested that oseltamivir and zanamivir are effective in reducing body temperature, while oseltamivir led to better clinical improvement regarding influenza-like symptoms in patients with COPD.

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 pandêmica A (H1N1) 2009: fatores de risco para o internamento / Pandemic influenza A (H1N1) 2009: risk factors for hospitalization

OBJETIVO: Avaliar os aspectos da influenza pandêmica A (H1N1) 2009 em pacientes hospitalizados a fim de identificar os fatores de risco para o internamento e, consequentemente, para o agravamento da doença. MÉTODOS: Estudo observacional e retrospectivo realizado entre março e dezembro de 2010. Os dados foram coletados a partir do Sistema Nacional de Agravos de Notificação do Ministério da Saúde. Foram incluídos somente os pacientes hospitalizados e não hospitalizados com confirmação laboratorial da infecção durante o período de estudo. As variáveis referentes às características demográficas e clínicas foram avaliadas estatisticamente a fim de comparar as taxas de internamento na presença ou na ausência desses fatores. Os fatores de risco foram identificados por regressão logística. RESULTADOS: Foram incluídos no estudo 4.740 pacientes com confirmação laboratorial da infecção. Desses, 1.911 foram internados, e 258 (13,5 por cento) foram a óbito. Os fatores de risco para o internamento foram idade (faixa etária de 20 a 29 anos), etnia negra ou indígena, presença de algumas comorbidades (cardiopatias, pneumopatias, nefropatias, hemoglobinopatia, imunodepressão, diabetes, obesidade, puerpério e tabagismo), número alto de comorbidades associadas, e alguns sintomas (dispneia, diarreia, vômito, dor torácica, hemoptise, pneumonia e sibilos). Níveis maiores de escolaridade e uso precoce do oseltamivir foram relacionados a fatores de proteção. A hospitalização contribuiu para o aumento da sobrevida. CONCLUSÕES: O conhecimento das características epidemiológicas que podem estar associadas a internação, gravidade da doença e mortalidade podem ser úteis na adoção de medidas preventivas e no diagnóstico e tratamento precoce da doença, colaborando para a diminuição dos óbitos e da necessidade de hospitalização.

OBJECTIVE: To evaluate pandemic influenza A (H1N1) 2009 in hospitalized patients in order to identify risk factors for hospitalization and, consequently, for the worsening of the disease. METHODS: This retrospective observational study was conducted between March and December of 2010. The data were collected from the Brazilian Ministry of Health National Case Registry Database. We included only patients (inpatients and outpatients) in whom H1N1 infection was confirmed (via laboratory testing) during the study period. The variables regarding demographic and clinical characteristics were statistically evaluated in order to compare the hospitalization rates in the presence or absence of these factors. Risk factors were identified by logistic regression analysis. RESULTS: We included 4,740 patients with laboratory confirmation of H1N1 infection. Of these, 1,911 individuals were hospitalized, and 258 (13.5 percent) died. The risk factors for hospitalization were age (20-29 years), African or Indigenous ethnicity, presence of specific comorbidities (heart disease, lung disease, kidney disease, hemoglobinopathy, immunosuppression, diabetes, obesity, puerperium, and smoking), a high number of comorbidities, and specific symptoms (dyspnea, diarrhea, vomiting, chest pain, hemoptysis, pneumonia, and wheezing). Higher levels of education and early use of oseltamivir were found to be protective factors. Hospitalization contributed to an increase in survival. CONCLUSIONS: Knowledge of the epidemiological characteristics that can be associated with hospitalization, disease severity, and mortality can be helpful in the adoption of preventive measures, as well as in the early diagnosis and treatment of disease, which might contribute to the reduction in the numbers of hospitalizations and deaths.

Costo-efectividad en la detección de influenza H1N1: datos clínicos versus pruebas rápidas / Cost-effectiveness in the detection of influenza H1N1: clinical data versus rapid tests

OBJETIVO: Evaluar el desempeño de los datos clínicos y la prueba rápida (PR) en el diagnóstico de influenza H1N1, y analizar el costo-beneficio que representa el uso de esta herramienta diagnóstica. MÉTODOS: Se aplicó la PR a pacientes que acudieron a cuatro hospitales en la ciudad de México con sintomatología similar a influenza (SSI) durante el período octubre y noviembre de 2009. Se comparó el desempeño diagnóstico de la SSI más la PR contra el de la reacción en cadena de la polimerasa en transcripción reversa en tiempo real (rRT-PCR). La rRT-PCR fue procesada en un laboratorio de referencia y cegado al resultado de la PR. Además, se llevó a cabo una evaluación económica a partir de la cual se estimó el impacto presupuestal relacionado con la utilización de la PR RESULTADOS: Se incluyó a 78 pacientes, de los cuales 39 fueron positivos para influenza H1N1 y 6 para influenza A estacional, de acuerdo al resultado de la rRT-PCR. La SSI mostró una sensibilidad de 96 por ciento y una especificidad de 21 por ciento, la PR de 76 por ciento y 82 por ciento y el conjunto de SSI más PR de 96 por ciento y 100 por ciento, respectivamente. El Cociente de Verosimilitud positivo de la SSI-cefalea fue de 31,5 y el de SSI-odinofagia fue de 330. El uso de PR mostró un ahorro de US$ 12,6 por cada caso sospechoso. CONCLUSIONES: El uso de la PR como auxiliar en el diagnóstico de influenza H1N1 incrementa la certeza y reduce el costo promedio por paciente sospechoso e infectado.

OBJECTIVE: Evaluate the performance of clinical data and the rapid influenza diagnostic test (RIDT) in diagnosing influenza H1N1, and analyze the cost-benefit of using this diagnostic tool. METHODS: The RIDT was used for patients who came to four hospitals in Mexico City with an influenza-like illness (ILI) in October and November 2009. The diagnostic performance of the ILI clinical data and the RIDT was compared to that of the real-time reverse transcription polymerase chain reaction (rRT-PCR) test. The rRT-PCR test was conducted in a reference laboratory and blinded to the results of the RIDT. An economic evaluation also was conducted to estimate the budgetary impact of using the RIDT. RESULTS: The study included 78 patients, 39 of whom tested positive for influenza H1N1 and 6 tested positive for seasonal influenza A, according to the results of the rRT-PCR. The ILI clinical data yielded a sensitivity of 96 percent and specificity of 21 percent; the RIDT yielded a sensitivity of 76 percent and specificity of 82 percent; and the ILI clinical data and RIDT together yielded a sensitivity of 96 percent and specificity of 100 percent. The positive likelihood quotient for ILI-headaches was 31.5 and that of ILI-odynophagia, 330. The use of RIDT yielded savings of US$12.6 per each suspected case. CONCLUSIONS: Use of the RIDT to aid in the diagnosis of influenza H1N1 increases certainty and lowers the average cost per suspected and infected patient.

Hospitalización por influenza en un Servicio de Pediatría de Santiago de Chile, 2001-2005 / Hospitalization due to influenza in children in Santiago, Chile, 2001-2005

Background: Influenza cause high hospitalization rates and complications in children. Objective: To describe clinical and epidemiological characteristics of influenza infection in hospitalized children. Patients and methods: In Universidad Católica Hospital, all hospitalizations due to influenza in children aged 15 days to 14 years, ocurring between January 2001 and December 2005 were reviewed. Results: Of a total of 3570 admissions associated with a respiratory illness, 124 (3.5 percent) were due to influenza, of which 75 percent presented between the months of April and June. Median age was 20.5 months (60 percent younger than 2 years) and 24 percent had an underlying risk factor. Most common symptoms were fever (94 percent) and dry cough (61 percent) and 75 percent of the children required oxygen. The most frequent complication was pneumonia (53 percent). The mean duration of hospitalization and oxygen use were 4.4 and 2.5 days respectively. Fifty two children (49.1 percent) received an antibiotic and nine children were admitted to intensive care unit. No deaths were recorded. Conclusion: Influenza virus cause serious complications and affects mostly healthy children younger than 2 years.

Introducción: El virus influenza produce elevadas tasas de hospitalización y complicaciones en niños. Objetivo: Describir el perfil clínico-epidemiológico de los niños hospitalizados por influenza en un hospital universitario. Pacientes y Métodos: Estudio descriptivo de las hospitalizaciones respiratorias y por influenza entre enero 2001 y diciembre 2005 en el Hospital Clínico de la Pontificia Universidad Católica. Resultados: Se hospitalizaron 3.570 niños por alguna causa respiratoria, 124 (3,5 por ciento) correspondieron a influenza confirmada, 75 por ciento ocurrieron entre abril y junio. La edad promedio fue 20,5 meses (60 por ciento) < 2 años), 24 por ciento tenían algún factor de riesgo identificado. Los síntomas más frecuentes fueron: fiebre (94 por ciento) y tos seca (61 por ciento). El 75 por ciento) presentó hipoxemia, siendo la complicación más frecuente la neumonía (53 por ciento). El promedio (días) de hospitalización y oxígeno fue 4,4 y 2,5; respectivamente. En 52/109 se indicaron antibacterianos, 9 niños ingresaron a cuidados intensivos. No hubo fallecidos. Conclusión: La hospitalización por influenza se asoció a serias complicaciones y afecta especialmente a niños sanos menores de 2 años.

La prevención de la influenza: recomendaciones para la temporada de 2005-2006 / Preventing influenza: recommendations for the 2005-2006 season

Influenza is a serious health problem worldwide due to the epidemics and pandemics that it periodically causes. The Advisory Committee on Immunization Practices (ACIP) of the United States of America recently published updated recommendations for influenza prevention and control for the 2005-2006 season. Many of these guidelines are of interest to the countries of the Region of the Americas, particularly those related to vaccination, which is the mainstay for preventing and controlling this disease. Various changes have been made in the recommendations that were published in 2004. First, the ACIP recommends vaccination against influenza for persons with any condition (e.g., cognitive dysfunction, spinal cord injury, seizure disorder, or other neuromuscular disorder) that can compromise respiratory function or make eliminating respiratory secretions difficult or that can increase the risk for aspiration. Second, the ACIP strongly recommends that all health care workers be vaccinated against influenza annually and encourages facilities that employ health care workers to vaccinate them by using approaches that maximize immunization rates. Third, the ACIP encourages the use of both available vaccines (inactivated and live, attenuated influenza vaccine (LAIV)) for eligible persons every influenza season, especially persons in recommended target groups. When inactivated virus vaccine is in short supply, the use of LAIV is especially encouraged, if feasible, for eligible persons (including health care workers) because such use might considerably increase the availability of inactivated virus vaccine for persons in high-risk groups. Fourth, the 2005-06 trivalent vaccine virus strains are A/California/7/2004 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Shanghai/361/2002-like antigens. For the A/California/7/2004 (H3N2)-like antigen, manufacturers may use the antigenically equivalent A/ New York/55/2004 virus, and for the B/Shanghai/361/2002-like antigen, manufacturers may use the antigenically equivalent B/Jilin/20/2003 virus or B/Jiangsu/10/2003 virus.

Infección respiratoria por virus influenza en niños: ¿Qué aprendimos durante el año 2004? / Clinical features of respiratory infections due to influenza virus in hospitalized children

Background: Infants and toddlers have the highest influenza hospitalization rate in pediatrics. Although the impact of this virus in children has been recognized, there is no defined statement related to vaccination in this population. Aim: To describe clinical and epidemiological characteristics of complicated influenza infections in hospitalized children. Material and methods: All hospitalizations due to influenza virus were recorded prospectively between March and June 2004. Results: We registered 40 laboratory-confirmed influenza admissions. Median age was 24 months (range: 15 days-14.5 years), 52% males, 18 younger than 2 years. Most of them had an underlying medical condition. The most common conditions were recurrent wheeze in 17, a neurological disease in 7 and asthma in 6. Twenty had more than one condition and 15 were previously healthy. The average days of respiratory symptoms and fever prior to admission were 5 and 3, respectively. The most common discharge diagnoses were concomitant viral-bacterial pneumonia in 53%, viral pneumonia in 38% and laryngitis in 8%. Influenza virus A was identified in 34/40 children. Oxygen supplementation was required by 34 cases; 20% of which required an O2 inspired fraction over 40%. The average days of hospitalization and oxygen were 4 and 3, respectively. Eleven children were treated with amantadine and 21 with antimicrobials. Four children were admitted to pediatric intensive care units and two cases required non-invasive ventilatory support. No deaths were recorded. Conclusions: Our data confirms the importance of influenza virus infection in children, as measured by admission rates, complications and length of hospital stay. Young children are a risk group for which immunization is recognized as protective.