Epidemiological survey on the benefit of neuraminidase inhibitors on severe acute respiratory syndrome due to COVID-19 / Levantamento epidemiológico do benefício de inibidores de neuraminidase na síndrome respiratória aguda grave por COVID-19 / Encuesta epidemiológica del beneficio de inhibidores de neuraminidase en síndrome respiratorio agudo severo por COVID-19

Background and objectives: The COVID-19 pandemic and its consequent severe acute respiratory syndrome (SARS) have taken the lives of millions since 2020. The use of neuraminidase inhibitors is a promising alternative in treating this disease, with several studies on off-label use being conducted since the beginning of the pandemic, but none of them have a large sample size and analyze multiple risk factors. The purpose of this article is to identify possible associations between various factors and risk of hospitalization, need for ventilation and death, as well as the influence of the prescription of Zanamivir and Oseltamivir on these same indicators. Methods: In this transversal study, approximately 900,000 medical records from all regions of Brazil were collected from the Ministry of Health database, and after that, proper statistical analysis of the variables was performed. Results: Hospitalization was associated with gender, ethnicity, education, local urbanization, State, and its percentage of elderly, as well as the climate. The prescription of Zanamivir and Oseltamivir was associated with higher incidence of symptoms, lower hospitalization and death rate, and lower need for invasive and non-invasive ventilation. Medical records from146,160 patients were excluded due to SARS not caused by COVID-19. Conclusion: From this data, it is possible to draw a risk profile for hospitalization by SARS and consider the use of Zanamivir and Oseltamivir as a treatment for these patients.(AU)

Justificativa e objetivos: A pandemia de COVID-19 e sua consequente síndrome respiratória aguda grave (SRAG) levaram milhões de pessoas a óbito desde 2020. O uso de inibidores da neuraminidase é uma alternativa promissora no tratamento dessa doença, com vários estudos sobre o uso off-label sendo conduzidos desde o início da pandemia, mas nenhum que tenha um grande tamanho amostral e que analise vários fatores de risco. O objetivo deste artigo é identificar possíveis associações entre diversos fatores e risco de hospitalização, necessidade de ventilação e óbito, assim como a influência da prescrição de Zanamivir e Oseltamivir nos mesmos indicadores. Métodos: Neste estudo transversal, foi feito o levantamento de aproximadamente 900 mil prontuários de todas as regiões do Brasil, provenientes de dados do Ministério da Saúde, e em seguida foi realizado o tratamento estatístico adequado das variáveis. Resultados: A hospitalização foi associada a sexo, etnia, escolaridade, urbanização do local, Estado e porcentagem de idosos do mesmo, assim como o clima. Já a prescrição de Zanamivir e Oseltamivir foi associada a maior incidência de sintomas, menor taxa de hospitalização e óbito e menor necessidade de ventilação invasiva e não-invasiva. Foram excluídos 146.160 prontuários devido a SRAG não ocasionada pela COVID-19. Conclusão: Com esses dados, é possível traçar um perfil de risco para hospitalização por SRAG e considerar o uso de Zanamivir e Oseltamivir como tratamento para esses pacientes.(AU)

Justificación y objetivos: la pandemia Covid-19 y su consiguiente síndrome respiratorio agudo severo (SRAS) han muerto millones de personas desde 2020. El uso de inhibidores de la neuraminidasa es una alternativa prometedora en el tratamiento de esta enfermedad, con varios estudios sobre el uso off-label que se realiza desde el principio de la pandemia, pero ninguno que tenga un tamaño de muestra grande y analice múltiples factores de riesgo. El propósito de este artículo es identificar posibles asociaciones entre varios factores y el riesgo de hospitalización, necesidad de ventilación y muerte, así como la influencia de la prescripción de Zanamivir y Oseltamivir en los mismos indicadores. Métodos: En este estudio transversal, se encuestaron a los datos del Ministerio de Salud de aproximadamente 900,000 registros de todas las regiones de Brasil, después de que se realizó un tratamiento estadístico adecuado de las variables. Resultados: La hospitalización se asoció con género, etnia, educación, urbanización del sitio, Estado y porcentaje de ancianos, así como el clima. La prescripción de zanamivir y oseltamivir se asoció con la mayor incidencia de síntomas, menor hospitalización y tasa de mortalidad y menor necesidad de ventilación invasiva y no invasiva. Se excluyeron 146,160 registros médicos debido a SRAS no causado por Covid-19. Conclusión: con estos datos, es posible dibujar un perfil de riesgo para la hospitalización por SRAS y considerar el uso de zanamivir y oseltamivir como tratamiento para estos pacientes.(AU)

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.

Abordaje diagnostico terapéutico de la neumonía viral grave / Diagnostic therapeutic approach to severe viral pneumonia

La guía de referencia rápida tiene como objetivo proporcionar al usuario las recomendaciones clave de la guía. Abordaje diagnóstico y terapéutico de la neumonía viral grave, seleccionadas con base a su impacto en salud por el grupo desarrollador, las cuales pueden variar en función de la intervención de que se trate, así como del contexto regional o local en el ámbito de su aplicación.

Detection of influenza B viruses with reduced sensitivity to neuraminidase inhibitor in Morocco during 2014/15 season

We monitored phenotypic and genotypic susceptibility of influenza viruses circulating in Morocco during 2014-2015 to oseltamivir and zanamivir. Throat and nasal swab specimens were collected from outpatients [with influenza-like illness] and inpatients [with severe acute respiratory illness] and tested for influenza viruses using real-time reverse transcription polymerase chain reaction. Positive samples were inoculated in MDCK cells and virus phenotypic susceptibility to neuraminidase inhibitors [NAIs] was assessed using fluorescent NA inhibition. Of 440 specimens, 135 were positive for influenza B Yamagata-like virus, 38 were A[H1N1] pdm09 and 25 were A[H3N2]. Sixty influenza B viruses isolated from MDCK cells showed no significant resistance to NAIs. However, two of these strains, B/Morocco/176H/2015 and B/Morocco/CP10/2015, showed reduced susceptibility to oseltamivir. The two influenza B viruses with reduced susceptibility to oseltamivir show that ongoing NAI susceptibility surveillance is essential

Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children

BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVE: To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments. METHODS Search methods: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database. Selection criteria: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza. Data collection and analysis: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers. MAIN RESULTS: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage ...

Uso de oseltamivir durante la pandemia de gripe a (H1N1): análisis de las reacciones adversas reportadas al sistema nacional de farmacovigilancia de ANMAT / Use of oseltamivir during influenza A (H1N1) pandemic: analysis of adverse reactions reported to the ANMAT national pharmacovigilance system

INTRODUCCIÓN: Oseltamivir es un medicamento antiviral usado para profilaxis y tratamiento de la gripe. Sus efectos adversos son conocidos a través de los ensayos clínicos y por la experiencia adquirida en la última epidemia de gripe aviar. Dentro de las reacciones más graves se han reportado casos de anafilaxia, eventos cutáneos y manifestaciones psiquiátricas como alucinaciones, delirium e ideación suicida. OBJETIVO: en julio de 2009, el departamento de Farmacovigilancia de ANMAT lanzó el Plan Nacional de Farmacovigilancia para Drogas Antivirales con el objetivo de recolectar mayor información de seguridad de estos medicamentos durante su uso masivo, con especial atención a las manifestaciones cutáneas, hepáticas y neuropsiquiátricas. MÉTODOS: se analizaron todas las notificaciones recibidas durante junio - noviembre de 2009. Los datos considerados fueron: sexo, edad, notificador, modalidad terapéutica, severidad, clasificación delefecto adverso principal e imputabilidad asignada. RESULTADOS: serecibieron 179 notificaciones, la mayoría asociadas a la modalidad tratamiento. Las reacciones adversas más reportadas involucraron al sistema gastrointestinal, siendo en su mayoría leves y autolimitadas. Con respecto a los casos psiquiátricos reportados, su severidad y variabilidad obliga a prestar especial atención a estas notificaciones. Se reportaron además casos de prolongación del Intervalo QTc, evento no descripto previamente en la literatura. CONCLUSIÓN: Dada la escasa experiencia en la Argentina y el estrecho perfil de seguridad de este fármaco, es indispensable continuar con una vigilancia activa del mismo.

INTRODUCTION: Oseltamivir is an antiviral drug used for profhylaxis and treatment of influenza. Adverse effects are known through clinical trials and in large part by the experience gained after its use in the last outbreak of avian influenza in Asia. Among the most serious reactions are reported cases of anaphylaxis, cutaneous events and psychiatric symptoms such as hallucinations, delirium and suicidal behaviour. OB JECTIVE: in line with various international regulatory authori ties, during July 2009, the ANMAT through Pharmacovigilance Department launched the National Pharmacovigilance Plan for antiviral drugs used for prophylaxis and treatment of the pandemic H1N1 influenza virus. The plan called for reporting any signs or symptoms, paying particular attention to the cutaneous, hepatic and neuropsychiatric symptoms. METHOD:we analyzed all reports received during June to November 2009. The data considered were: sex, age, notifier, therapeutic modality, severity, classification of main side effect and imputation assigned. RESULTS: 179 notifications were received, most associated with treatment modality. As can be seen world wide, in Argentina, the great majority of reported adverse reactions involve the gastrointestinal system, being mostly mild and self-limiting. Given the variability and severity of psychiatric cases reported it is very important to pay close attention to these reports. Reported cases include the QTc interval prolongation, an event not previously described in the literature. CONCLUSIONS: it is essential to continu e with proactive monitoring of this drug because of the limited current experience and the benefits/ risks ratio of the safety profile of this drug.

Tratamiento y profilaxis de influenza estacional en niños / Treatment and prophylaxis of seasonal influenza in children

Influenza es una enfermedad respiratoria que produce una importante morbi-mortalidad. La prevención más importante es la vacuna anti-influenza. El tratamiento debe indicarse en las formas moderadas a graves, en niños con factores de riesgo e inmunosuprimidos. El tratamiento es efectivo si se inicia antes de las 48 horas del comienzo de los síntomas. Los inhibidores de la neuraminidasa como oseltamivir y zanamivir son efectivos e indicados para su uso en influenza en niños. Oseltamivir esta indicado a partir del año de edad y zanamivir en mayores de 7 años como tratamiento y mayores de 5 años como profilaxis. Ambos acortan los días de enfermedad, evitan la diseminación de la enfermedad y disminuyen complicaciones como la neumonía. En influenza B la eficacia es menor. La resistencia a estos agentes es baja.