Select Committee on Science and Technology Fourth Report


CHAPTER 5: MITIGATION

Stopping a pandemic reaching the United Kingdom

5.1.  So far we have focused on either preventing a pandemic by targeting avian influenza, or on the possibility that a potential pandemic could be averted by isolating the region of origin and targeting the population with antiviral drugs. However, there is no guarantee that these strategies will succeed. Modelling shows that if a new and highly infectious virus were to spread beyond its region of origin, and particularly if a cluster of cases were to occur in an urban centre, it would rapidly become difficult, if not impossible, to prevent a global pandemic. This chapter therefore focuses on the measures that the Government may be tempted to introduce in order to slow or mitigate the impact of such a pandemic.

5.2.  In the case of the SARS outbreak in 2003 measures taken in various countries included:

It is likely that there will be pressure to introduce some or all of these measures in the event of an outbreak of pandemic influenza. The question is, will they have any effect?

5.3.  SARS vividly demonstrated the speed with which infection can travel around the globe along the path of major air routes. There will be an obvious temptation, in the event of an outbreak of pandemic influenza in south east Asia, to impose restrictions on air travel from the affected area. However, even in the case of the 1918-19 pandemic, Australia, through stringent maritime isolation and quarantine, succeeded only in securing a more protracted, milder outbreak. Since then international travel has expanded beyond all recognition, and there are now approaching two billion passenger journeys by air each year. In addition, travel via third countries is commonplace.

5.4.  To be effective travel restrictions would have to be rigorous, and would involve huge economic cost. Expert opinion is that a reduction of international travel by 90 percent would only achieve a small delay in spread of the disease. Indeed, modelling of the development of a pandemic in the United Kingdom shows that reducing the number of imports of infection from 10 to one a day would succeed only in deferring the peak of a pandemic by around a week, while reducing the number of new cases per day at the peak from around 1.2 million to a million:

FIGURE 2

Predicted course of an influenza pandemic in the UK (ten imports per day compared with one import per day)


Source: Professor Neil Ferguson. "Day" starts from introduction of first case to the UK. Assumes a reproduction rate of 1.8. Also see note to Figure 1 (p. 11).

5.5.  Blanket quarantining of arrivals from affected regions might be more effective in slowing down imports of the disease, and the United States government already has a number of quarantine stations that could be used in the event of a pandemic. However, the costs would again be very considerable, regardless of the implications for civil liberties. There is also a risk that were quarantine arrangements to be announced many travellers would find ways to avoid quarantine by entering the country via unaffected third countries.

5.6.  Another strategy employed by some countries to restrict the spread of SARS was the thermal screening of arrivals at airports, allowing in theory for the identification and isolation of those with early symptoms of infection. However, recent research suggests that such screening would have very limited effect in detecting early infection with influenza, which has no symptoms and leaves body temperature unchanged.[11]

Mitigating the effects: antiviral drugs

5.7.  If the virus were to be introduced into the United Kingdom, various strategies could be used to mitigate its effects and limit or slow down its spread. The most promising of these involve the use of antiviral drugs either to treat those infected with influenza or as prophylaxis for those who are at risk of infection. The options were summarised at our seminar by Professor Ferguson:

5.8.  The backdrop to all these options is the Government's order of 14.6 million courses of the antiviral drug oseltamivir (Tamiflu). This order, which will be fulfilled by autumn 2006, is based on the assumption that the disease will have a 25 percent "attack rate"—in other words, that one quarter of the population will be infected, and that for each person infected one course of the drug will be required.

5.9.  A "treatment-only" approach is thus the Government's preferred option. Assuming that the virus does not develop resistance to the drug, cases would be less severe, and hospitalisation and mortality correspondingly lower. However, for the drug to have an effect the course has to start within 48 hours of the onset of symptoms—the earlier the better. At the peak of pandemic, with around one million new cases each day, there would be huge strains on the health service in diagnosing new cases and getting drugs to patients within this timescale. We look at this issue in more detail in our next chapter. In addition, we are seriously concerned over the robustness of the assumptions made regarding the "attack rate" of a new virus, which in reality could be either significantly below or above 25 percent. If the latter were to be the case, supplies would simply run out.

5.10.  At the other extreme, blanket prophylaxis does not appear feasible. Antivirals provide protection only as long as they are being taken, and each course of oseltamivir lasts five days. It would be prohibitively expensive for the whole population to be provided with antiviral drugs until such time as a vaccine was available against the pandemic strain, possibly up to nine months after the initial outbreak. Even if this approach were affordable, the limited supply of antivirals globally would prevent it.

5.11.  Targeted or "household" prophylaxis in the initial stages of a pandemic falls between the two extremes of blanket prophylaxis and treatment-only. We have already noted that antivirals are particularly effective when taken preventatively. The object of limited prophylaxis would thus be to target the first cases, identifying close contacts (such as family members and healthcare workers) and prescribing antivirals in such a way as to slow down the spread of the disease. In principle this could buy more time which could be used for the development of a vaccine.

5.12.  At our seminar Professor Ferguson estimated that "household prophylaxis" could lead to a reduction of around 30 percent in the number of cases of infection over the first 180 days of a pandemic. The HPA were more tentative, but accepted that if the first importation of the virus could be identified targeted prophylaxis "might just slow [the virus] down for a few weeks which gives us time". However, in the absence of evidence from well-conducted trials, or the experience of an actual epidemic, these projections remain somewhat speculative. (Q 116)

5.13.  Despite the views of the HPA, the Government have not publicly committed themselves to using antiviral drugs as prophylaxis to target the first cases. The Minister, indeed, said in terms that "we believe that this should be used for treatment and not used prophylactically". The Contingency Plan, while noting that "short term prophylaxis" could be used to delay the establishment of a pandemic, states that this would be "done on a case by case basis and is … not the main use of antiviral drugs" (p. 46). Moreover, whereas the Government's order for 14.6 million courses leaves little or no spare capacity for prophylactic use, a strategy of "household prophylaxis" would require from 30 to 100 percent more antivirals than are currently on order. Not only would there be significant cost implications, but there could be a substantial delay between an order being made and the delivery of the drugs. (Q 222)

5.14.  "Household prophylaxis" could also be combined with limits on public gatherings, for instance the closure of schools or workplaces, suspension of football matches, and so on. Targeted at the initial outbreaks, such additional measures could significantly delay the spread of the disease, albeit at the expense of considerable social disruption. The Contingency Plan simply states that they are "being kept under review" (p. 48). It is worth noting that under the terms of the Civil Contingencies Act 2004 the Government have very wide powers in the event of a national emergency (which could include a pandemic) to take steps of this kind at short notice.

5.15.  There is an overarching issue of cost. The Government have committed £200 million to the existing order for oseltamivir. The drug has a limited shelf-life (five years), so if there is no pandemic within this time-frame the stockpile will have to be discarded and (assuming the world remains on pandemic alert) replaced. Yet so far as we were able to ascertain from the Minister this commitment has been made without any cost benefit analysis (see QQ 222-223). It is difficult to predict what such analysis would reveal—it might show that household prophylaxis, although more expensive in absolute terms, represented a more cost-effective strategy than treatment-only. In the absence of comprehensive modelling of the best and most cost-effective way to use antiviral drugs, the Government's open-ended commitment of considerable sums to their purchase is a matter of serious concern.

5.16.  Finally, there remains the possibility that the virus could develop resistance to oseltamivir. We have already alluded to the fact that some H5N1 strains in south east Asia have developed resistance to M2 inhibitors such as amantadine, and that research is being undertaken into the optimum combinations of antiviral drugs in order to minimise further development of resistance. Although there is no confirmed case of resistance to oseltamivir, it would be prudent for the Government to consider a back-up plan, possibly involving zanamivir (Relenza) or combination use of oseltamivir with M2 inhibitors.

CONCLUSIONS

5.17.  Once an influenza pandemic is established, in south east Asia or elsewhere, there is no realistic prospect of preventing its spread to the United Kingdom. Travel restrictions, quarantine or screening at airports, while they would be highly visible, would only delay the spread of the virus.

5.18.  The early and targeted use of antiviral drugs, not only to treat the first cases in this country, but to provide prophylactic protection to close contacts such as family members or health workers, could both delay and lower the peak of a United Kingdom pandemic. This would reduce the strain on health services, and give more time for the production of a vaccine.

5.19.  We are therefore extremely concerned at the lack of clarity in the Government's policy on prophylactic use of antiviral drugs, and at the possibility that the Government's order of only 14.6 million courses of oseltamivir may have tied them into a treatment-only policy on using the stockpile.

5.20.  We recommend that the Government work together with the HPA and the research community to establish the optimal strategy for the use of antiviral drugs, and that further orders, if required, should as a matter of urgency be placed to allow this strategy to be implemented. We further recommend that this strategy should incorporate a rigorous cost-benefit analysis.

5.21.  We recommend that the Government develop back-up plans in case resistance to oseltamivir emerges. These should encompass possible combination therapies or the acquisition of reserve stocks of zanamivir.


11   "Entry screening for severe acute respiratory syndrome (SARS) or influenza: policy evaluation", BMJ 2005;331:1242-1243 (September 2005). Back


 
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