BMJ  2007;334:268-269 (10 February), doi:10.1136/bmj.39101.628715.80

Editorials

Preparing for the next flu pandemic

New clinical guidelines focus on coordinating services and standardising care

In the past three years, the incidence of infection with the H5N1 variant of avian flu has increased in humans in southeast Asia during periods corresponding to winter and spring in the northern hemisphere.¹ More cases of H5N1 infection in humans increase the chances that the virus will adapt towards efficient transmission between humans and therefore of a flu pandemic.

The United Kingdom is well advanced in its preparations for a flu pandemic.² The British Infection Society, British Thoracic Society, Health Protection Agency, and Department of Health have recently developed and published provisional guidelines on the clinical management of pandemic flu.³ These guidelines cover the clinical management of children and adults with flu during a pandemic.

In interpandemic years when influenza is circulating in the community, presentation with acute fever and new (or in chronic lung disease, worsening) cough is highly predictive of flu in adults.⁴ In a pandemic, key predictive features may change as a result of altered thresholds for consultation, symptom presentation, and clinical features. If this occurs, an updated clinical definition will be released by the Health Protection Agency, informed by guidance from the World Health Organization.

Randomised controlled trials, cohort studies, and modelling studies show that antiviral agents, if given promptly, can reduce the length of illness, viral secretions, and complications; these agents may also reduce peak clinical attack rates.^{5 6} The UK government has stockpiled enough oseltamivir for 25% of the population to be treated; if the clinical attack rate is higher then antivirals will have to be prioritised to risk groups.

Previous pandemics have shown that secondary bacterial complications (particularly pneumonia) have a high morbidity and mortality.^{7 8 9} Antibiotic treatment for Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae should be considered at first consultation for adults who have serious worsening of symptoms or fever that does not start to subside after 48 hours, and for patients with chronic obstructive pulmonary disease or other severe comorbid disease (or both). Doxycycline or co-amoxiclav are recommended³ in the community and in patients in hospital who are not severely ill.

Patients referred to hospital are likely to require management of worsening comorbid disease, such as cardiac failure or flu related pneumonia. Bilateral x ray changes in flu related pneumonia raise the possibility of primary viral pneumonia, which has a poor prognosis and should be treated as severe pneumonia.³ Indications for transfer to critical care are no different in a pandemic, although limited resources will require effective triage and difficult ethical decisions.

In children, as in adults, fever, cough, and rhinorrhoea are cardinal symptoms of flu, but infants may simply be febrile and non-specifically unwell. Children should be given fluids, antipyretics (avoid aspirin), and antivirals—oseltamivir in liquid form can be prescribed for children aged 1-7 years.³ Infants under 1 year are a particular problem. They have a higher risk of hospital admission and secondary bacterial infection,¹⁰ and oseltamivir is not indicated on the basis of central nervous system toxicity and mortality in infant rats, which is assumed to reflect immaturity of the blood-brain barrier. Infants therefore need to be assessed by a doctor, and the threshold for antibiotic treatment should be low. Those with underlying cardiac or respiratory disease, the immunocompromised, and the non-ambulant are also at increased risk of complications and should receive early antibiotics. Co-amoxiclav is recommended for children under 12 years.³

These clinical guideline recommendations are informed by data from seasonal flu and previous pandemics.³ As with all pandemic plans, uncertainties are acknowledged. In particular, the virus strain and its disease potential in terms of clinical spectrum of illness, spread, and severity of illness are unknown. Furthermore, the susceptibility profile to current antiviral agents cannot be guaranteed, as discussed by Tsiodras and colleagues in this week's BMJ.¹¹ Other uncertainties relate to the epidemiology of pathogens that may have a role in secondary infections. Flu related pneumonia occurs in up to a fifth of cases; these cases are often associated with Staphylococcus aureus and have a worse outcome.^{12 13} Community acquired strains of methicillin resistant Staphylococcus aureus (MRSA) are currently relatively uncommon in Europe and the UK, but are of increasing concern in the United States.¹⁴ A change in the epidemiology of this infection in Europe could have important consequences in the event of a flu pandemic.

These guidelines will need to be revised in accordance with updated clinical and epidemiological data. Currently the pandemic alert status stands at phase 3 (human infection with a new flu virus subtype but no, or limited, human to human spread). If WHO raises the pandemic alert status to phase 5, the last of the three pre-pandemic phases (large cluster(s) of human cases and virus better adapted to humans), the guidelines will be updated.

In the meantime these guidelines will help to plan stockpiling of essential resources, coordination of services, and standardisation of care. They also provide the framework for national, regional, and local operational guidelines that take account of and detail the actions needed in the face of limited resources.

¹ Nottingham University Hospitals, Nottingham NG5 1PB, ² John Radcliffe Hospital Oxford, Oxford OX3 9DU, ³ University of Southampton, Southampton SO17 1BJ

---

Competing interests: None declared.

Provenance and peer review: Non-commissioned, not externally peer reviewed.

References

1. Epidemiology of WHO-confirmed human cases of avian influenza A(H5N1) infection. Wkly Epidemiol Rec 2006;81:249-57.[Medline]
2. Mounier-Jack S, Coker RJ. How prepared is Europe for pandemic influenza? Analysis of national plans. Lancet 2006;367:1405-11.[CrossRef][ISI][Medline]
3. Provisional guidelines from the British Infection Society, British Thoracic Society and Health Protection Agency in collaboration with the Department of Health. Pandemic flu: the clinical management of patients with an influenza-like illness during an influenza pandemic . Thorax J Infect
4. Call SA, Vollenweider MA, Hornung CA, Simel DL, McKinney WP. Does this patient have influenza? JAMA 2005;293:987-97.[Abstract/Free Full Text]
5. Ferguson NM, Cummings DA, Fraser C, Cajka JC, Cooley PC, Burke DS. Strategies for mitigating an influenza pandemic. Nature 2006;442:448-52.[CrossRef][Medline]
6. Kaiser L, Wat C, Mills T, Mahoney P, Ward P, Hayden F. Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Arch Intern Med 2003;163:1667-72.[Abstract/Free Full Text]
7. Anon. Some aspects of the recent epidemic of influenza in Dundee. BMJ 1958;1:908-13.[ISI][Medline]
8. Abrahams A, Hallows N, French H. Influenzo-pneumococcal and influenzo-streptococcal septicaemia: epidemic influenzal "pneumonia" of highly fatal type and its relation to "purulent bronchitis". Lancet 1919;1:1-11.
9. Schwarzmann SW, Adler JL, Sullivan RJ Jr, Marine WM. Bacterial pneumonia during the Hong Kong influenza epidemic of 1968-1969. Arch Intern Med 1971;127:1037-41.[CrossRef][ISI][Medline]
10. Neuzil KM, Zhu Y, Griffin MR, Edwards KM, Thompson JM, Tollefson SJ, et al. Burden of interpandemic influenza in children younger than 5 years: a 25-year prospective study. J Infect Dis 2002;185:147-52.[CrossRef][ISI][Medline]
11. Tsiodras S, Mooney J, Hatzakis A. The role of combined antiviral therapy in pandemic influenza. BMJ 2007 doi: 10.1136/bmj.39105.428981.BE[Free Full Text]
12. Oswald NC, Shooter RA, Curwen MP. Pneumonia complicating Asian influenza. BMJ 1958;2:1305-11.[ISI][Medline]
13. Robertson L, Caley JP, Moore J. Importance of Staphylococcus aureus in pneumonia in the 1957 epidemic of influenza A. Lancet 1958;2:233-6.[ISI][Medline]
14. Hageman JC, Uyeki TM, Francis JS, Jernigan DB, Wheeler JG, Bridges CB, et al. Severe community-acquired pneumonia due to Staphylococcus aureus, 2003-4 influenza season. Emerg Infect Dis 2006;12:894-9.[ISI][Medline]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Articles

Bird flu and transparency

Fiona Godlee
BMJ 2007 334: 0. [Extract] [Full Text]

The next best thing

Douglas Kamerow
BMJ 2007 334: 0. [Extract] [Full Text]

Role of combination antiviral therapy in pandemic influenza and stockpiling implications

Sotirios Tsiodras, John D Mooney, and Angelos Hatzakis
BMJ 2007 334: 293-294. [Extract] [Full Text] [PDF]