El escándalo de la cloroquina / The chloroquine scandal

El autor aborda el caso de la cloroquina y la hidroxicloroquina en el contexto de la actual pandemia de COVID-19, a través de dos ejes centrales. Por un lado, el escándalo a nivel editorial y de comunicación de la evidencia, y por otro, el de la toma de decisiones en salud pública. Describe flagrantes debilidades en la cadena de generación, difusión y aplicación del nuevo conocimiento. Adicionalmente, explora iniciativas y propuestas que podrían contribuir a solucionar estos problemas. (AU)

The author addresses the case of chloroquine and hydroxychloroquine in the context of the current COVID-19 pandemic, through two central axes. On the one hand, the scandal at the editorial and communication level of the evidence, and on the other, that of decision-making in public health. He describes flagrant weaknesses in the chain of generation, diffusion,and application of new knowledge. Additionally, it explores initiatives and proposals that could contribute to solving these problems. (AU)

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benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments.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 ...

Virological surveillance and antiviral resistance of human influenza virus in Argentina, 2005–2008 / Vigilancia virológica y resistencia a los antivíricos del virus de la gripe humana en la Argentina, 2005–2008

Objective. To describe the virological characteristics of the influenza strains circulating in Argentina in 2005–2008 and to assess the prevalence of antiviral resistance. Methods. On the basis of their geographical spread and prevalence, influenza A and B isolates grown in Madin–Darby canine kidney cells were selected after antigenic and genomic characterization to be analyzed for antiviral resistance by enzymatic assay and pyrosequencing. Amantadine susceptibility was evaluated by pyrosequencing for known resistance markers on 45 strains of influenza A. Susceptibility to oseltamivir and zanamivir was evaluated by enzymatic assay of 67 influenza A and 46 influenza B strains, some of which were further analyzed by sequencing the neuraminidase gene. Results. Resistance to amantadine was observed only on A(H3N2) strains (29/33); all of them carried the mutation S31N in their M2 sequence. Oseltamivir resistance was observed in 12 (34.3%) of the 35 A(H1N1) strains from 2008; all of them carried the mutation H275Y in their neuraminidase sequence. All these viruses remained sensitive to zanamivir. Conclusions. This study describes a high incidence of amantadine-resistant influenza A(H3N2) viruses since 2006 and an unprecedented increase in oseltamivir resistance detected only in influenza A(H1N1) viruses isolated in 2008. Influenza A and B viruses were more sensitive to oseltamivir than to zanamivir, and influenza A viruses were more sensitive to both neuraminidase inhibitors than the influenza B viruses. The national data generated and analyzed in this study may help increase knowledge about influenza antiviral drug resistance, which is a problem of global concern.

Objetivo. Describir las características virológicas de las cepas de virus de la gripe que circulaban en la Argentina entre el 2005 y el 2008, y evaluar la prevalencia de la resistencia a los antivíricos. Métodos. Según su diseminación geográfica y su prevalencia, se seleccionaron aislados de gripe A y B cultivados en células renales caninas de Madin-Darby después de su caracterización antigénica y genómica, y se analizó su resistencia a los antivíricos mediante análisis enzimático y pirosecuenciación. La sensibilidad a la amantadina se evaluó por pirosecuenciación para los marcadores conocidos de resistencia en 45 cepas de gripe A. La sensibilidad al oseltamivir y al zanamivir se evaluó mediante análisis enzimático de 67 cepas de gripe A y 46 cepas de gripe B, algunas de las cuales se analizaron en mayor profundidad mediante la secuenciación del gen de la neuraminidasa. Resultados. Se observó resistencia a la amantadina solo en las cepas de gripe A (H3N2) (29/33); todas ellas tenían la mutación S31N en su secuencia de M2. Se observó resistencia al oseltamivir en 12 (34,3%) de las 35 cepas de gripe A (H1N1) aisladas en el 2008; todas ellas tenían la mutación H275Y en su secuencia de neuraminidasa. Todos estos virus conservaron su sensibilidad al zanamivir. Conclusiones. En este estudio se describe una incidencia elevada del virus de la gripe A (H3N2) resistente a la amantadina desde el 2006 y un aumento sin precedentes de la resistencia al oseltamivir detectada solo en los virus de la gripe A (H1N1) aislados en el 2008. Los virus de la gripe A y B fueron más sensibles al oseltamivir que al zanamivir y los virus de la gripe A fueron más sensibles a ambos inhibidores de la neuraminidasa que los virus de la gripe B. Los datos nacionales generados y analizados en este estudio pueden ayudar a aumentar los conocimientos acerca de la resistencia a los fármacos antivíricos dirigidos contra el virus de la gripe, lo que es un motivo de preocupación mundial.

Prevalence of oseltamivir-resistant 2009 H1N1 influenza virus among patients with pandemic 2009 H1N1 influenza infection in NRITLD, Tehran, Iran

Oseltamivir-resistant cases were reported during the 2009 pandemic influenza outbreak and therefore, widespread emergence of oseltamivir-resistant 2009 H1N1 virus is imaginable. Underlying medical conditions like immunosuppression increase the chance of oseltamivir resistance. In a retrospective cross-sectional study, respiratory tract specimens of confirmed cases of 2009 H1N1 influenza referred to the Masih Daneshvari Hospital were analyzed for presence of H275Y mutation. From November 2009 through March 2010, oseltamivir-resistant 2009 H1N1 infection was observed and confirmed in 4 patients [including 2 immunocompromised patients] by performing H275Y mutation molecular testing. Close monitoring of resistance to neuraminidase inhibitors is essential in tertiary care centers. The H275Y mutation [oseltamivir-resistant genotype] could appear in the absence or presence of selective drug pressure

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.

Novel Influenza A (H1N1): Where Are We?

No abstract available.

[Actualities on the avian influenza]

Influenza viruses cause yearly seasonal outbreaks and are periodically involved in the emergence of new subtypes causing pandemics. Wild birds are considered as the natural host of these viruses. At the present time, we are facing the progressive expansion of an H5N1 virus appeared in South-East Asia and affecting an increasing number of countries, the last one beeing Turkey. This highly pathogenic strain in birds passed from poultry to humans, resulting in a mortality of approximately 50%. Person-to-person transmission seems to be very scarce, most of patients were contamined by affected poultry. Compared to normal influenza, human infection by H5N1 virus is frequently associated with digestive symptoms and respiratory failure resulting from viral pneumonia. Diagnosis relies mainly on viral isolation and genomic tests performed in a biosafety level 3 laboratory. The most effective control measure is to eliminate animal source, which remains beyond reach. Antiviral therapy is available [neuraminidase inhibitors] and immunization trials with experimental vaccine are pending. Nevertheless, the massive needs for these products are hampered by limited production capacities and costs. According to WHO recommendations, Tunisia elaborated a preparedness plan and reinforced virological surveillance of both human and animal influenza. Efforts are needed to enhance the production of antiviral drugs and vaccines in order to be able to contain the future H5N1 pandemic influenza

Influenza: una revisión de su quimioprofilaxis y terapéutica anti viral / Influenza: chemoprophylaxis and antiviral treatment

Diferentes agentes antivirales están disponibles para ser utilizados de manera profiláctica o terapéutica en las infecciones por el virus influenza. Los inhibidores de la neuraminidasa viral tienen la ventaja de actuar eficazmente sobre el virus A y B de la influenza, logrando un mejor espectro antiviral que la actividad restringida sobre el virus A presente en amantadina y rimantadina. El espectro antiviral de estas moléculas junto a la evidencia disponible en los diversos ensayos de eficacia clínica, respaldan el uso de estos fármacos para acortar la enfermedad y disminuir la severidad y complicaciones de la influenza. La eficacia de zanamivir y oseltamivir para este propósito es similar y ambas presentan reacciones adversas menores propias de la vía de administración nasal u oral que debe emplearse en cada caso. No obstante estas ventajas, el costo de estos medicamentos es elevado y limita su aplicación hacia el escenario terapéutico, especialmente en pacientes de alto riesgo. En situaciones donde la limitación económica es importante, amantadina en dosis apropiada, puede todavía ser considerada como una alternativa costo-efectiva para el manejo de los pacientes con influenza o para la intervención en grupos de riesgo no vacunados