The Pharmaceutical Journal
Vol 274 No 7333 p78
22 January 2005

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Influenza — the calm before the storm?

Last week levels of influenza-like illnesses in England reached the highest levels seen this winter, triggering media claims of an imminent epidemic. However, strategies adopted in recent years may have made this less likely — except when the world looks east. Hannah Pike (on the staff of The Journal) investigates

Reports of influenza-like illnesses in the community increased last week, leading the media to claim that the health service should brace itself for an epidemic. However, figures from the Health Protection Agency surveillance unit show that flu levels are still low for this time of year. In fact, UK health protection strategies have been remarkably successful to date. The main threat of a pandemic now comes from the recent development of avian flu in the Far East.

Monitoring flu levels in the UK is co-ordinated by the Communicable Disease Surveillance Centre at the Health Protection Agency in Colindale. The centre receives weekly reports from separate schemes in England (from the Royal College of General Practitioners), Wales (National Public Health Service) and Scotland (Health Protection Scotland), using networks of GPs to record consultations for flu-like illnesses. The centre also collates virological data from laboratory systems and community-based sampling schemes across the UK.

Last week reported cases of influenza-like illness across England reached 41 per 100,000 GP consultations. Carol Joseph, a consultant clinical scientist in epidemiology at the HPA, explained that although this value is the highest seen this winter, levels of 30–200 per 100,000 consultations are regarded as normal seasonal activity. A level of below 30 per 100,000 consultations is considered to be baseline, and levels above 200 per 100,000 are regarded as an epidemic.

Levels were highest in the north of England last week (62 per 100,000). Levels in central and southern England were 39 and 30 per 100,000 respectively. In Wales, the rate for influenza consultations increased to 8.28 per 100,000 last week from 2.3 per 100,000 the week before. Levels in Scotland remained below the Scottish baseline (50 per 100,000) at 41 per 100,000. Baseline values vary between countries because of different recording and reporting methods.

In the rest of Europe last week, influenza-like illness cases were only reported to exceed national baselines in Belgium and Spain. Flu activity was also medium to low in most of the rest of the world. Factors contributing to these low levels compared with recent years may include the success of government vaccination campaigns, improvements in air quality, reduced smoking, and increased awareness of hygiene measures.

Virological data have shown that predominant strain this season is the A/Wellington/ 1/2004 (H3N2)-like virus, superseding the A/Fujian/411/2002 (H3N2)-like virus that was responsible for most cases of flu last year.

John Watson, head of respiratory diseases at the HPA, commented: “Flu activity is unpredictable. We are unable to anticipate when we are likely to see a peak in activity or how great the peak will be. Nevertheless, flu activity generally continues for eight to 12 weeks in this country once it has begun.”

Dr Joseph added that, judging by rates of flu activity in the past, levels would be expected to peak in three to four weeks’ time.

Last week the Department of Health sent a letter to health professionals, stating that, in line with National Institute for Clinical Excellence guidance, the use of oseltamavir, zanavir and amantadine for the prevention or treatment of influenza is now recommended (see Panel). This letter is circulated whenever the incidence of reported influenza-like illness in England exceeds the baseline value, and it is known that influenza is circulating in the community.

Last week the HPA published a report entitled “A winter’s tale” (PDF 600K)that looks at the impact of winter illnesses on the community, GP practices, hospitals and mortality. Douglas Fleming, director of the Birmingham Research Unit at the Royal College of General Practitioners and one of the authors of the report, pointed out that when considering the effects on the health service, it is also important to know which age groups of people are being affected. The report states that, for example, from 1989–2001 more than 50 per cent of winter hospital admissions thought to be associated with flu outbreaks occurred in people over 75 years of age, accounting for 69 per cent of total bed occupancy. In last week’s figures, the highest rates in England were seen in the 15–44 year age group (51 consultations per 100,000) and the 45–64 year age group (41 per 100,000).

Dr Joseph said that last year most of the recorded flu activity occurred in the 0–4 year old age group, a group that is not routinely vaccinated. She said that data suggest that although the elderly populations are now well protected by vaccinations, the younger at risk population is still under-protected, and is therefore likely to be targeted for next year’s vaccination programme.

The report also says that the impact of acute bronchitis is at least as great as that of flu, although the cause of the disease is not known. It highlights this as a priority for research. It also says that near patient tests for influenza and respiratory syncytial virus should now be evaluated in clinical settings since they are of high enough quality for aiding decisions regarding hospital admissions.

Planning for a pandemic

A pandemic is a worldwide epidemic that could be caused when a flu virus undergoes what is known as an antigenic shift and emerges as a new strain to which people have little or no immunity.

Three principle pandemics occurred last century, in 1918, 1957 and 1968. The largest, the Spanish influenza epidemic of 1918, caused an estimated 20 to 40 million deaths worldwide.

In the next few months the Department of Health is expected to publish draft new proposals for action in case of a flu pandemic. The proposals, which will apply to the whole of the UK, will form an update to the “Multiphase contingency plan for pandemic influenza”, published by the DoH in 1997.

The current plan outlines the central role of health departments in case of a pandemic (see Panel) and provides a framework for the development of more detailed local plans. The DoH told The Journal: “Pandemic influenza is one of the infectious disease contingencies that the Department of Health plans for. The overarching UK plan is currently being brought up to date, and we are working closely with international organisations, researchers and industry to develop our plans. This includes looking at issues such as the role of antivirals and vaccines as well as other public health measures which could help slow the spread of a pandemic.”

The current plan states that health authorities are responsible for the planning and implementation of local contingency arrangements and notes that pharmacists may need to be involved in the development of local plans. Regarding community pharmacy the plan says: “Community pharmacists will need to anticipate increased demand for home treatments, such as simple linctus and antipyretics, and for a wider range of prescriptions, including antibiotics and oxygen. Reminders of the association of salicylates and influenza with Reye’s syndrome in children under 12 years of age should be considered.”

The current plan says that doctors will be advised of national policy for the use of antiviral medicines depending on the type of pandemic in question, any known resistance and the availability of the drugs. In the case of worldwide demand the drugs are likely to be in short supply and will be restricted to those in whom they may be life-saving or to those in vital occupations. Stockpiling of antiretrovirals is only possible to a limited extent because of the shelf lives of the drugs.

Although it is not yet clear which sections of the plan are to be updated or rewritten, a DoH spokeswoman told The Journal that the new proposals will draw on experience gained from Asia with outbreaks of severe acute respiratory syndrome and avian flu.

In a recent issue of Science, Klaus Stöhr, co-ordinator of the World Health Organization influenza programme wrote that the outbreak of avian flu in Asia has rendered the world closer to a new pandemic. “Three to four influenza pandemics have occurred each century and there is no reason to believe this century will be spared,” he says. He says that vaccines would be the best line of defence against high morbidity and mortality associated with a flu pandemic, but pointed out that vaccines have never been used to a large extent during a pandemic, even in 1957 and 1968 when seasonal vaccinations were already established. Reasons for this were based on the small time scale available for interventions, he says, such as inadequate surveillance systems, limited vaccine production capacity and uncertain regulatory pathways.

Dr Stöhr says that many of these technical obstacles have now been overcome. He points out that case reporting and surveillance systems are now more reliable and national and international licensing agencies have now published safety and efficacy requirements for pandemic vaccines.

Dr Stöhr says that although capacity for influenza vaccine production has doubled over the past 10 years, it is still insufficient to meet a huge global demand. He says that research is under way into techniques to produce vaccines rapidly in case of a pandemic. “A major breakthrough has been development of laboratory methods to design pandemic vaccine prototype strains rapidly and with predictable characteristics, such as the absence of avian pathogenicity,” he says, “This allows vaccine production in eggs and compliance with biosafety requirements for production plants.”

In a recent letter to Nature, researchers from the Harvard School of Public Health wrote that compared with many other infectious diseases, the influenza pandemic of 1918 was not especially contagious. Rather, the high rate of mortality was caused by the large number of people susceptible to that strain at that time.

The rate of transmission of infectious diseases is measured by the reproductive number, the number of secondary cases of the disease caused by each primary case. By combining a special model with data from pneumonia and influenza death epidemic curves from 45 US cities, the researchers estimate that the reproductive number for the 1918 pandemic was around two to three. They say that this is not a high figure relative to the transmission of other influenza subtypes or other infectious diseases. In principle, they say, a similar pandemic could be prevented by vaccinating or administering prohpylaxis to 50–75 per cent of the population. However, they note that current capacity for vaccine production and stocks of antiviral medicines are not sufficient to do this. Furthermore, they say that control measures that were used to control the SARS outbreak, for example, such as isolation, will be of minimal use in an influenza outbreak because substantial transmission of the virus occurs before patients display any symptoms.

Avian flu is a contagious disease caused by subtypes H5 or H7 of the influenza A virus that has been in existence for more than 100 years. In its severe form it is rapidly fatal and affected birds can die on the same day they develop symptoms. In 1997, however, the first cases of the disease being transferred to humans was reported in Hong Kong. The strain of the virus was H5N1, which is closely related to the human influenza virus. It is now known that the virus can affect humans who come into contact with infected material such as droppings from affected birds.

The main concern is that the H5N1 virus may combine with the human influenza virus to form a new strain that is transmissible from human to human. If that were to happen, a pandemic would be likely. The resultant disease would be as contagious as human flu and as deadly as avian flu. Humans currently have no immunity to avian flu, and its mortality is much higher than that of SARS, even though the number of humans affected is small.

Dr Stöhr says: “For the first time in history the virus subtype of a possibly looming pandemic is known, and a vaccine against it could be stored for immediate use at the start of efficient human-to-human transmission. WHO is therefore recommending creation of national and international stockpiles of H5N1 vaccine, for emergency use in affected areas and as a defence strategy for slowing international spread.”

“Slow progress of influenza pandemic vaccine development is no longer caused by insurmountable technical hurdles,” says Dr Stöhr. “The hurdles are political and economic in nature. Uncertainty over a viable market prevents companies from investing in pandemic vaccine development, and many governments see no reason to step in as availability of pandemic vaccines is not considered a public health good.”