Preventing and treating influenza

WHO estimates that seasonal influenza epidemics result in three to five million cases of severe illness and 250 000 to 500 000 deaths each year in the industrialised world alone. Although vaccination remains the most important measure for reducing this sizeable public health burden, the influenza virus neuraminidase inhibitors, zanamivir and oseltamivir, have been welcomed as long awaited additional tools for treatment and prevention. However, in terms of meeting public health objectives, which include clinical effectiveness in high risk groups and preparedness for the next influenza pandemic, they have important limitations.

As documented in the paper by Cooper et al p 1235) in this issue, neuraminidase inhibitors are clinically effective for the treatment of influenza in otherwise healthy adults and children as well as for prevention of the disease.¹ When used as a treatment, they can reduce the duration of uncomplicated disease by about one day, and the likelihood of complications requiring antimicrobial treatment. Taken prophylactically they can decrease the likelihood of developing influenza by 70-90% depending on the target population and duration of use. Baseline data for the surveillance of viral susceptibility to neuraminidase inhibitors have been established—initial data have produced no evidence of naturally occurring resistance in any of the isolates tested.²

Despite these promising features many obstacles limit the role of neuraminidase inhibitors as public health tools. High cost is one factor. Another obstacle is the paucity of data on efficacy in preventing serious influenza related complications and mortality in groups at highest risk, including elderly people and people with underlying disease—the groups responsible for the greatest medical and economic burden of influenza and hence of greatest public health concern.

Neuraminidase inhibitors were introduced into clinical practice from 1999 to 2002 but are currently used in only a few countries. In view of their limitations they are only adjuncts to influenza vaccination. Around three quarters of all prescriptions are issued in Japan, with the remainder concentrated in the United States and only a very small number issued elsewhere. Oseltamivir is by far the most widely used neuraminidase inhibitor, mainly because of ease of application.

Community studies show that seasonal prophylactic use of neuraminidase inhibitors in healthy adults, administered after exposure in households and in residential care, would be clinically effective. However, when economic factors are considered vaccination seems to have a much more favourable ratio of cost to benefit.³

Because of costs and an efficacy that also depends on the prevalence of influenza in the population, neuraminidase inhibitors are recommended for treatment only during the influenza season when most infections of the upper respiratory tract are due to influenza viruses. Such a strategy automatically excludes most countries in tropical areas, where sporadic cases of influenza occur year round with no distinct season. In addition, countries in temperate areas require efficient community based virological surveillance schemes to indicate to general practitioners the beginning of the influenza season. Rapid influenza tests are available. However, their lack of sensitivity limits their use to the influenza season.

For all these reasons, currently available neuraminidase inhibitors cannot replace annual influenza vaccination, which remains the most effective means of reducing the medical and economic impact of influenza. Unfortunately knowledge about the medical benefits of influenza vaccination and its favourable cost:benefit ratio compared with other prevention strategies has not been translated into effective immunisation programmes in most countries. At present, only around 50 countries, mainly in the industrialised world, have policies for influenza immunisation, and vaccination coverage often reaches only 10-20% of people in groups at high risk. Coverage rates in developing countries are often negligible. In addition, immunisation coverage of healthcare workers in direct contact with elderly people is often low despite strong evidence of their role in contributing to institutional outbreaks as well as their own vulnerability to infection.

Recognising the significance of influenza immunisation as a public health strategy, the World Health Assembly of the World Health Organization has in May 2003 approved a resolution calling on countries that have national influenza vaccination policies to implement strategies to increase vaccination coverage of all people at high risk to at least 50% by 2006 and 75% by 2010. Countries without national influenza vaccination policies should assess the disease burden and economic impact of annual influenza epidemics as a basis for framing and implementing influenza prevention policies within the context of other national health priorities.⁴

Considering the annual death toll and morbidity from influenza and the need for efficient and affordable antivirals during the first phase of the next influenza pandemic, cost efficient and clinically effective treatment and prophylactic tools are urgently needed. Neuraminidase inhibitors are clinically effective complements to the current influenza intervention tools. However, costs and lack of data on their effectiveness in the groups most severely affected by influenza limit their use in many industrialised countries and make them largely unaffordable in developing countries. Promising research is under way to develop new neuraminidase inhibitors that are more efficacious, cost less, and are simpler to prescribe. It is to be hoped that they are available before the next pandemic strikes.