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Document "Use of antiviral agents and other measures in an influenza pandemic": English Abstract
Influenza viruses give rise to epidemics virtually every year and they occasionally also lead to pandemics (i.e. epidemics on a global scale). Unlike the epidemics, influenza pandemics are, to a great extent, unpredictable. Thus although it is generally expected that another influenza pandemic will occur, we cannot predict when this will be. Furthermore, if a pandemic arises abroad it is difficult to predict how long it will be before it reaches our own country. And once it has arrived here, we can only make a partial estimate of how many people will fall ill, which population groups are at greater risk and which individuals, being ill, run a greater risk of complications.
The massive incidence of avian influenza in South-East Asia appears to have increased the risk that a virus strain may emerge that is capable of triggering an influenza pandemic. In preparation for a possible pandemic, the Dutch government has begun to build up a stock of compounds known as neuraminidase inhibitors for use as antiviral agents. On 24 February 2004 the Health Council published the interim advisory report Antiviral agents in an influenza pandemic, in which the Committee responsible for preparing the advisory report indicated the measures that it believes would need to be taken if such a pandemic were to reach the Netherlands in the not-too-distant future, and particularly if there were to be a shortage of antiviral agents. In this second advisory report, the Committee puts the recommendations from the interim advisory report into a broader context. The objectives underlying the Committees recommendations here are the same as in the interim advisory report, namely: to distribute the pandemic over time by reducing the number of infected people and clinical cases and to contain the impact of infection by means of antiviral therapy with neuraminidase inhibitors.

General measures

The Committee reaffirms its medically based recommendation from the interim advisory report that, for the duration of the pandemic, schools should be closed down and events at which large numbers of people gather in a confined space should be cancelled. The Committee realises that this measure would have major social and economic consequences. It therefore understands that the decision to close schools will depend on the anticipated severity and extent of the pandemic, which would largely be determined by the characteristics of the virus (for example its pathogenicity and the speed at which it spreads).
The Committee regards vaccination against influenza as the best means of protecting the population against an influenza pandemic. Should vaccine stocks prove inadequate, the Committee recommends that priority should be given to the particular groups defined in its interim advisory report (i.e. people who fall into a [pandemic-specific] risk group and professionals).
The Committee also recommends that risk groups should not be vaccinated against pneumococci during an influenza pandemic, since there is no evidence that pneumococcal vaccination confers protection in these groups.

Use of neuraminidase inhibitors in the first clinical cases

When the first clinical cases are recorded, it is likely that outbreaks will be isolated and affect a small number of patients only. If this is the case, and if these patients are traced shortly after they fall ill, the Committee recommends treating the patient and administering postexposure prophylaxis (neuraminidase inhibitors after exposure  or possible exposure  but before clinical symptoms have emerged) to his/her family or household and other close contacts. The aim here is to slow down the pandemic or even to nip it in the bud. The Committees advice is that these measures should even be adopted when stocks of neuraminidase inhibitors are limited (as is the case at present). This is an extension of the recommendation made in the interim advisory report, where the Committee advocated treatment only (both of the patient and his/her family or household).

Use of neuraminidase inhibitors in a manifest pandemic or in the event of the large-scale introduction of virus from abroad

During a manifest pandemic, the Committee recommends that any resident of the Netherlands displaying a clinical picture that resembles influenza should be treated with neuraminidase inhibitors  preferably as soon possible, but no later than 48 hours after the onset of the first clinical symptoms. This approach serves to mitigate the course of the disease and helps patients to build up immunity to the virus, meaning that they will not fall ill (or at least that they will be far less affected) in the event of a second infection. The Committees advisory report implies that stocks of neuraminidase inhibitors need to be expanded to such an extent that there is enough to treat all residents of the Netherlands with influenza. Since it is estimated that up to 30 percent of the population could become ill during a pandemic, the Committee anticipates that a total stock of five million courses of the neuraminidase inhibitor oseltamivir is sufficient.
The Committee does not even advocate prophylaxis in the presence of adequate stocks of neuraminidase inhibitors, because then protection would only be conferred for as long as the compound is used. After the therapy is stopped, the person would still be vulnerable to the virus owing to a lack of immunity. During a manifest pandemic, however, the Committee can envisage that the neuraminidase inhibitors might be used prophylactically in particular groups or under particular circumstances. What it has in mind here are patients whose immune system is compromised (e.g. as a result of bone marrow transplantation) or the occurrence of influenza in a department of a care home or nursing home that can easily be isolated. The Committee recommends that the decision on whether to administer prophylaxis should be left to the individual patients attending physician.

Comments

The Committee regards the procurement of a sufficiently large stock of neuraminidase inhibitors as just one of the elements required in order to prepare for the use of these compounds during a pandemic. The Committee does not believe that its remit includes a detailed elaboration of the logistical implications of its recommendations. It therefore confines itself to noting that the success of the use of neuraminidase inhibitors will depend to a great extent on the way in which this strategy is implemented.
The Committee is not currently in a position to quantify the cost-effectiveness of its recommendations (e.g. in terms of the cost per quality-adjusted life-year). It believes that there are too many uncertainties  not only of a factual nature (e.g. the timing of the pandemic and the characteristics of a future pandemic virus) but also uncertainties that can only be eliminated through (possibly arbitrary) policy choices. The Committee provides a summary of the elements that feature in an evaluation of cost-effectiveness, but feels that it is not incumbent upon it to make these choices.

The Committees recommendations are based on the current, limited, state of knowledge. Its advice is therefore that its recommendations should be kept in line with advances in knowledge and that the opinion of experts should be sought when making decisions on what action is to be taken (for example from the new centre for infectious disease control).
The chances of gaining some insight into the pandemic will improve if it begins abroad and only reaches the Netherlands after some time has elapsed. Use can then be made of data from the countries that have already been affected.

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