The 2009 Influenza A (H1N1) Pandemic—A Blast from the Past


Japan, was approved during the pandemic in the US as an emergency endovenous drug only, being markedly inferior to zanamivir in cases of OVR but with only mild to moderate adverse events related to its use. Along with laninamivir, peramivir is in the final phases of clinical studies.20,50


ORV is still rare, with rates of 2.5% in Europe.7,53,54 OVR is


secondary to mutation A His275Tyr in the neuraminidase glycoprotein and is related to immunosuppression and prolonged post-exposure prophylaxis, the latter being the most important. Nevertheless, wild-type cases have been reported.53


OVR should be suspected when


viral shedding or symptomatic disease persists after completion of an oseltamivir treatment regimen.8


were frequently used in critically ill patients.


There is proven evidence of NIs reducing the severity and duration of influenza symptoms.21,55


The greatest benefit was seen when therapy


was initiated within the first 48 hours, reflected in lower rates of complicated disease (severe disease, prolonged hospital stay, ICU admission and mortality) for both healthy and high-risk patients; however, a recent meta-analysis failed to establish a clear association. Oseltamivir treatment was associated with a reduction in the need for antibiotic therapy.55


and virological benefit was seen for seasonal influenza;10 have been published in children infected with H1N1v.20


With delayed initiation (up to 96 hours), a clinical similar results Delayed receipt


of antiviral therapy was independently associated with severe disease and a high risk for death (OR 2.9, 95% CI 0.3–28%), and was related to the need for high doses of oseltamivir and long periods of time before virus excretion was complete.8,34,37


Suspected and confirmed cases of influenza in pregnant women and after two weeks post-partum should be treated with antivirals. Pregnant women have been successfully treated with oseltamivir and, more recently, with inhaled zanamivir.17,22,56,57


There is a lack of data generated


by endovenous use of NIs. Ribavirin in combination with neuramidase inhibitors is not recommended. Further pharmacological studies in this group of pateints have been proposed, suggesting that with standard dosing, subtherapeutic treatment may occur owing to changes in renal and hepatic function during pregnancy.58


HIV-infected patients with


suspected or confirmed H1N1v infection must be empirically treated with antivirals; the clinical course in this group did not vary from that of


1. 2. 3. 4. 5. 6. 7.


Itho Y, et al., In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses, Nature, 2009;460: 1021–5.


Morens DM, et al., The persistent legacy of the 1918 influenza virus, N Engl J Med, 2009;361:225–9.


Morens DM, et al., The 1918 influenza pandemic: lessons for 2009 and the future, Crit Care Med, 2010;38:e10–e20.


Reed C, et al., Estimates of the prevalence of pandemic (H1N1) 2009, United States, April–July 2009, Emerg Infect Dis, 2009;15:2004–7.


Chowell G, et al., Severe respiratory disease concurrent with the circulation of H1N1 influenza, N Engl J Med, 2009;361:674–9.


Jain S, et al., Hospitalized patients with 2009 H1N1 influenza in the United States, April–June 2009, N Engl J Med, 2009;361:1935–44.


Rello J, Clinical review: primary influenza viral pneumonia, Crit Care, 2009;13:235.


8. WHO Writing Committee, Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection, N Engl J Med,


13. 10. 11. 12. 2010;362:1708–19. 9.


Nicoll A, A new decade, a new seasonal influenza: the Council of the European Union Recommendation on Seasonal Influenza Vaccination, Eurosurveillance, 2010. Available at: www.eurosurveillance.org/VIEWARTICLE. ASPX?ARTICLEID=19458 (accessed 14 June 2010).


Lee N, et al., Diagnosis, management and outcomes of adults hospitalized with influenza, Thorax, Jun 2010;65(6): 510–5.


Kumar A, et al., Critically ill patients with 2009 influenza A (H1N1) infection in Canada, JAMA, 2009;302:1872–9.


Mazick A, et al., Higher all-cause mortality in children during autumn 2009 compared with the three previous years: pooled results from eight European countries, Eurosurveillance, 2010. Available at: www.euro surveillance.org/ViewArticle.aspx?ArticleId=19480 (accessed 14 June 2010).


Pebody RG, et al., Pandemic influenza A (H1N1) 2009 and the mortality in the United Kingdom: risk factors for death, April 2009 to March 2010, Euro Surveill, 2010;15:19571.


Higher doses and prolonged treatment immunocompetent patients.8,48 In cases where seasonal H1N1 virus is


circulating concomitantly with pandemic H1N1, NIs should be given in combination with adamantanes.7


Ribavirin is being studied as a


co-therapy in influenza owing to evidence of in vitro effectiveness against H1N1, H3N2, and H5N1 strains when combined with oseltamivir. Interferon is not useful in the treatment of H1N1v infection; however, studies of its use as a chemoprophylactic drug are under way.20


A meta-analysis showed a large decrease in mortality associated with treatment with convalescent blood products.59,60,61


In cases where the


vaccine is not available (i.e. due to high demand/insufficient stock, or else) convalescent blood products might be a solution as an immunoprophilactyc option.61


Oseltamivir as extended post-exposure


chemoprophylaxis (ring chemoprophylaxis) was effective at reducing the reproductive number (from 1.95 to 0.11) and the overall proportion of infection in the population tested (from 6.4 to 0.6%), with no significant side effects.62


years of age for post-exposure prophylaxis.20,62 Respiratory Support


Non-invasive mechanical ventilation was not effective at preventing invasive mechanical ventilation in the majority of patients.27,63


As in


ARDS, protective and open-lung ventilation is recommended; neuromuscular blockade and the prone position can also be included in management. High-frequency oscillatory ventilation (HFOV) and airway-pressure-release ventilation (APRV) were rarely used, there were never any detrimental effects. In centres where ECMO was used, it was required for up to one-third of mechanically ventilated patients.7,47 Young adults, obese women, pregnant women, and post-partum women with ARDS secondary to viral pneumonitis were the most common groups to receive ECMO; only rarely did children and elderly patients undergo this technique. The mortality rate in patients receiving ECMO for ARDS owing to influenza H1N1v was lower than that seen for other causes of ARDS (23 versus 30–48%).42


2009 H1N1 Pandemic taught us a lesson; even though we are not yet able yet to predict this events, effective epidemiological surveillance, organization and quick interventions are essential in reducing negative consequences n


14.


European Centers for Disease Control and Prevention. Hospital surveillance – severe acute respiratory infection (SARI), 2010. Available at: www.ecdc.europa.eu (accessed 22 July 2010).


15. 16. 17. 18. 19.


WHO Press, Pandemic H1N1 2009 – Weekly Update 110, 21 July 2010. Available at: www.who.int (accessed 22 July 2010).


Munster VJ, et al., Pathogenesis and transmission of swine-origin 2009 A (H1N1) influenza virus in ferrets, Science, 2009;325:481–3.


Louie JK, et al., Severe 2009 H1N1 influenza in pregnant and postpartum women in California, N Engl J Med, 2010;362:27–35.


Kumar S, et al., Clinical and epidemiological characteristics of children hospitalized with 2009 pandemic H1N1 influenza A infection, Pediatr Infect Dis J, 2010;29:591–4.


Nguyen-Van-Tam JS, et al., Risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza: United Kigndom first wave (May–September 2009), Thorax, 2010;65:645–51.


Zanamivir is indicated in patients over five


US RESPIRATORY DISEASE


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