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H5N1 influenza pandemic: contingency plans

2005; Elsevier BV; Volume: 366; Issue: 9485 Linguagem: Inglês

10.1016/s0140-6736(05)67080-8

1474-547X

Kenneth WT Tsang, Philip Eng, Chong Kin Liam, Young‐Soo Shim, Wah Kit Lam,

Animal Disease Management and Epidemiology

The current epidemic of the highly pathogenic H5N1 strain of avian influenza, with a mortality of 58%, appears relentless in Asia, particularly in Vietnam and Thailand.1World Health Organization. Cumulative number of confirmed human cases of avian influenza A/(H5N1) since 28 January 2004. May 4, 2005.http://www.who.int/csr/disease/avian_influenza/country/cases_table_2005_05_04/en/index.htmlGoogle Scholar Although inefficient, there is some evidence of human-to-human transmission for the H5N1 virus.2Ungchusak K Auewarakul P Dowell SF et al.Probable person-to-person transmission of avian influenza A (H5N1).N Engl J Med. 2005; 352: 333-340Crossref PubMed Scopus (794) Google Scholar A possible catastrophic pandemic could, therefore, emerge should re-assortment of viral antigens occur resulting in a highly infectious strain of H5N1. Influenza pandemics in 1917–18, 1957–58, and 1968–69 have already caused approximately 15, 4, and 0·75 million deaths worldwide, respectively. A vaccine for H5N1 will not be available in the foreseeable months. Even if pharmaceutical manufacturing begins soon after an outbreak, there would not be a sufficient supply for the countries most in need—ie, the Asian nations. Antiviral drugs are consequently the only specific treatment, pending availability of effective vaccines. These include M2 inhibitors (amantadine and rimantadine), which are ineffective against H5N1 in vitro, and the neuraminidase inhibitors (oseltamivir and zanamivir).3Zeitlin GA Maslow MJ Avian influenza.Curr Infect Dis Rep. 2005; 7: 193-199Crossref PubMed Scopus (10) Google Scholar The neuraminidase inhibitors reduce the severity and duration of symptoms, and prevent clinical influenza as post-exposure and seasonal prophylaxis.4Kirkbride HA Watson J Review of the use of neuraminidase inhibitors for prophylaxis of influenza.Commun Dis Public Health. 2003; 6: 123-127PubMed Google Scholar Influenza contingency plans by the WHO and most governments generally advocate detection, isolation, staff protection, and the start of antiviral treatment for patients, and their contacts.5World Health Organization National influenza pandemic plans.http://www.who.int/csr/disease/influenza/nationalpandemic/en/Date: 2005Google Scholar Many governments, including those of Hong Kong, Thailand, Singapore, Malaysia, and Korea, have already stockpiled, at a very substantial expense, vast quantities of oseltamivir to prepare for an outbreak.5World Health Organization National influenza pandemic plans.http://www.who.int/csr/disease/influenza/nationalpandemic/en/Date: 2005Google Scholar Nonetheless, the efficacy of neuraminidase inhibitors, even for non-H5N1 influenza A in healthy people and taken within 48 h of disease onset, is only slight (table).6GlaxoSmithKline.Relenza datasheet. Issue number 5. June 8, 2000. Galxo Wellcome Production, Evreux, France2000http://www.msds-gsk.com/uk_presc/11057406.pdfGoogle Scholar, 7Hoffmann-La Roche.Tamiflu datasheet. Core data sheet version 1.5. May, 3 2004. F Hoffmann-La Roche, Basel2001http://www.medsafe.govt.nz/profs/Datasheet/t/Tamiflucapsusp.htmGoogle Scholar, 8The MIST (Management of Influenza in the Southern Hemisphere Trialists) Study Group. Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infections.Lancet. 1998; 352: 1877-1881Summary Full Text Full Text PDF PubMed Scopus (411) Google Scholar, 9Treanor JJ Hayden FG Vrooman PS et al.Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial.JAMA. 2000; 283 (US Oral Neuraminidase Study Group): 1016-1024Crossref PubMed Scopus (950) Google Scholar, 10McKimm-Breschkin JL Management of influenza virus infections with neuraminidase inhibitors: detection, incidence, and implications of drug resistance.Treat Respir Med. 2005; 4: 107-116Crossref PubMed Scopus (61) Google Scholar, 11Kiso M Mitamura K Sakai-Tagawa Y et al.Resistant influenza A viruses in children treated with oseltamivir: descriptive study.Lancet. 2004; 364: 759-765Summary Full Text Full Text PDF PubMed Scopus (697) Google Scholar The use of oseltamivir in five of the ten cases reported in Vietnam did not show any obvious clinical efficacy, and the mortality was 80% in this cohort.12Tran TH Nguyen TL Nguyen TD et al.Avian influenza A (H5N1) in 10 patients in Vietnam.N Engl J Med. 2004; 350: 1179-1188Crossref PubMed Scopus (746) Google Scholar The two neuraminidase inhibitors, oseltamivir and zanamivir, have not been directly compared in controlled trials. Their pharmacological properties are compared in the (table.6GlaxoSmithKline.Relenza datasheet. Issue number 5. June 8, 2000. Galxo Wellcome Production, Evreux, France2000http://www.msds-gsk.com/uk_presc/11057406.pdfGoogle Scholar, 7Hoffmann-La Roche.Tamiflu datasheet. Core data sheet version 1.5. May, 3 2004. F Hoffmann-La Roche, Basel2001http://www.medsafe.govt.nz/profs/Datasheet/t/Tamiflucapsusp.htmGoogle Scholar, 8The MIST (Management of Influenza in the Southern Hemisphere Trialists) Study Group. Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infections.Lancet. 1998; 352: 1877-1881Summary Full Text Full Text PDF PubMed Scopus (411) Google Scholar, 9Treanor JJ Hayden FG Vrooman PS et al.Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial.JAMA. 2000; 283 (US Oral Neuraminidase Study Group): 1016-1024Crossref PubMed Scopus (950) Google Scholar, 10McKimm-Breschkin JL Management of influenza virus infections with neuraminidase inhibitors: detection, incidence, and implications of drug resistance.Treat Respir Med. 2005; 4: 107-116Crossref PubMed Scopus (61) Google Scholar, 11Kiso M Mitamura K Sakai-Tagawa Y et al.Resistant influenza A viruses in children treated with oseltamivir: descriptive study.Lancet. 2004; 364: 759-765Summary Full Text Full Text PDF PubMed Scopus (697) Google Scholar Although both have similar efficacy, zanamivir has fewer adverse reactions, and a favourable resistance profile. The resistance factor would be an important consideration in a pandemic situation. The reasons for zanamivir not being chosen for stockpiling might include concern that young children and patients with intellectual or coordination impairments would not be able to inhale zanamivir properly, although there are novel ways of giving the drug to children.13Imuta F Toyoda M Toyoda T New application method of zanamivir with a straw.Pediatr Int. 2003; 45: 366-367Crossref PubMed Scopus (6) Google Scholar The occurrence of bronchospasm and reduced lung function is very rare, and patients with asthma and chronic obstructive pulmonary disease (COPD) seem to tolerate inhalation of zanamivir as well as the placebo.14Murphy KR Eivindson A Pauksens K et al.Efficacy and safety of inhaled zanamivir for the treatment of influenza in patients with asthma or chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled multicentre study.Clin Drug Invest. 2000; 20: 337-349Crossref Scopus (103) Google Scholar The inhaled flow rate needed to give the custom-designed inhaler for zanamivir (49–110 L/min) is similar to that for accuhaler (30–90 L/min), and turbohaler (60–90 L/min), which are popular dry-powder inhalation devices used by many asthmatic and COPD patients, even during exacerbations.15Cass LM Brown J Pickford M et al.Pharmacoscintigraphic evaluation of lung deposition of inhaled zanamivir in healthy volunteers.Clin Pharmacokinet. 1999; 36: 21-31Crossref PubMed Scopus (123) Google Scholar, 16Hill LS Slater AL A comparison of the performance of two modern multidose dry powder asthma inhalers.Respir Med. 1998; 92: 105-110Summary Full Text PDF PubMed Scopus (83) Google Scholar Therefore governments should also consider stockpiling zanamivir as an anti-influenza agent in their pandemic plans. Actual logistics for giving out antivirals to patients and close contacts need to be efficient and completed within 48 h. It seems more appropriate for community-based health-care personnel or even pharmacists, rather than hospital-based health-care workers, to handle such procedures.TableComparison of pharmacological properties of neuraminidase inhibitorsZanamivirOseltamivirAge approved for prophylaxis6GlaxoSmithKline.Relenza datasheet. Issue number 5. June 8, 2000. Galxo Wellcome Production, Evreux, France2000http://www.msds-gsk.com/uk_presc/11057406.pdfGoogle Scholar, 7Hoffmann-La Roche.Tamiflu datasheet. Core data sheet version 1.5. May, 3 2004. F Hoffmann-La Roche, Basel2001http://www.medsafe.govt.nz/profs/Datasheet/t/Tamiflucapsusp.htmGoogle Scholar>5 years>13 yearsAge approved for treatment6GlaxoSmithKline.Relenza datasheet. Issue number 5. June 8, 2000. Galxo Wellcome Production, Evreux, France2000http://www.msds-gsk.com/uk_presc/11057406.pdfGoogle Scholar, 7Hoffmann-La Roche.Tamiflu datasheet. Core data sheet version 1.5. May, 3 2004. F Hoffmann-La Roche, Basel2001http://www.medsafe.govt.nz/profs/Datasheet/t/Tamiflucapsusp.htmGoogle Scholar>5 years>1 yearRenal impairment6GlaxoSmithKline.Relenza datasheet. Issue number 5. June 8, 2000. Galxo Wellcome Production, Evreux, France2000http://www.msds-gsk.com/uk_presc/11057406.pdfGoogle Scholar, 7Hoffmann-La Roche.Tamiflu datasheet. Core data sheet version 1.5. May, 3 2004. F Hoffmann-La Roche, Basel2001http://www.medsafe.govt.nz/profs/Datasheet/t/Tamiflucapsusp.htmGoogle ScholarNo dose adjustment requiredAdjustment if creatinine clearance 10–30 mL/minHepatic impairment6GlaxoSmithKline.Relenza datasheet. Issue number 5. June 8, 2000. Galxo Wellcome Production, Evreux, France2000http://www.msds-gsk.com/uk_presc/11057406.pdfGoogle Scholar, 7Hoffmann-La Roche.Tamiflu datasheet. Core data sheet version 1.5. May, 3 2004. F Hoffmann-La Roche, Basel2001http://www.medsafe.govt.nz/profs/Datasheet/t/Tamiflucapsusp.htmGoogle ScholarNo dose adjustment requiredSafety not establishedReduction of influenza symptoms8The MIST (Management of Influenza in the Southern Hemisphere Trialists) Study Group. Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infections.Lancet. 1998; 352: 1877-1881Summary Full Text Full Text PDF PubMed Scopus (411) Google Scholar, 9Treanor JJ Hayden FG Vrooman PS et al.Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial.JAMA. 2000; 283 (US Oral Neuraminidase Study Group): 1016-1024Crossref PubMed Scopus (950) Google ScholarBy median of 1·5 dayBy median of 1·3 dayAdverse reactions6GlaxoSmithKline.Relenza datasheet. Issue number 5. June 8, 2000. Galxo Wellcome Production, Evreux, France2000http://www.msds-gsk.com/uk_presc/11057406.pdfGoogle Scholar, 7Hoffmann-La Roche.Tamiflu datasheet. Core data sheet version 1.5. May, 3 2004. F Hoffmann-La Roche, Basel2001http://www.medsafe.govt.nz/profs/Datasheet/t/Tamiflucapsusp.htmGoogle ScholarAllergy—very rareNausea 7·0–10·7%Bronchospasm andVomiting 2·1–8·0%dyspnoea—very rareDiarrhoea 3·2–5·5%Rash and urticaria—very rareBronchitis 0·7–3·7%Headache 1·6–20·1%Fatigue 0·8–7·9%Frequency of drug resistance after treatment10McKimm-Breschkin JL Management of influenza virus infections with neuraminidase inhibitors: detection, incidence, and implications of drug resistance.Treat Respir Med. 2005; 4: 107-116Crossref PubMed Scopus (61) Google Scholar, 11Kiso M Mitamura K Sakai-Tagawa Y et al.Resistant influenza A viruses in children treated with oseltamivir: descriptive study.Lancet. 2004; 364: 759-765Summary Full Text Full Text PDF PubMed Scopus (697) Google ScholarNone reported1·3 and 8·6–18·0% in adults and children, respectively Open table in a new tab Governments and health agencies should also consider planning for clinical trials, for instance a combination of both neuraminidase inhibitors, with or without other potential novel drugs, such as short-interfering RNAs and interferon.3Zeitlin GA Maslow MJ Avian influenza.Curr Infect Dis Rep. 2005; 7: 193-199Crossref PubMed Scopus (10) Google Scholar These trials, if initiated at the early stages of a pandemic, could provide useful information for further patient and outbreak management in later stages. The geographic location of vaccine manufacturers in developed countries would also delay poorer Asian nations from obtaining the updated influenza vaccine. Perhaps vaccine and neuraminidase inhibitor manufacturing activities should also begin in Asia to deal with such deficiencies. The ethics of maintaining drug patents in a potential worldwide catastrophe is questionable. Epidemiological modelling suggests that influenza is more infectious than severe acute respiratory syndrome, and that severe acute respiratory syndrome infection control measures might not be adequate for a pandemic of influenza.17Webby RJ Webster RG Are we ready for pandemic influenza?.Science. 2003; 302: 1519-1522Crossref PubMed Scopus (536) Google Scholar There will, therefore, be an overwhelming strain on health-care workers and hospitals in an H5N1 pandemic, and staff could be rapidly demoralised and degenerate into deserters, if colleagues develop hospital-acquired H5N1 infection, especially if not given adequate intensive-care unit treatment.18Tzeng HM Nurses' professional care obligation and their attitudes towards SARS infection control measures in Taiwan during and after the 2003 epidemic.Nurs Ethics. 2004; 11: 277-289Crossref PubMed Scopus (41) Google Scholar Protection of core personnel should also be planned to underpin recovery in the aftermath, when many key players in health care and governmental institutions would have perished. We have no conflict of interest to declare.