Antivirals drugs: their role during a pandemic

November 2005

Pending the availability of vaccines, several antiviral drugs are expected to be useful for prophylaxis (prevention of illness) or treatment purposes. Two drugs (in the neuraminidase inhibitors class), oseltamivir (commercially known as Tamiflu) and zanamivir (commercially known as Relenza), have been shown, in laboratory studies, to reduce the severity and duration of illness caused by seasonal influenza. The efficacy of the neuraminidase inhibitors depends on their administration within 48 hours after symptom onset. For cases of human infection with H5N1, the drugs may reduce the severity of disease and improve prospects of survival, if administered early, but clinical data are limited. The H5N1 virus is expected to be susceptible to the neuraminidase inhibitors.

Another class of antiviral drugs, the M2 inhibitors amantadine and rimantadine, could potentially be used against pandemic influenza, but resistance to these drugs may develop rapidly and this could significantly limit their effectiveness. Some currently circulating avian H5N1 strains are fully resistant to the M2 inhibitors, while others remain fully susceptible.

For the neuraminidase inhibitors, the main constraints – which are substantial – involve limited production capacity and a price that is prohibitively high for many countries. Because of the complex and time-consuming manufacturing process, the sole manufacturer of oseltamivir is unable fully to meet demand and faces a backlog of orders. At present manufacturing capacity, which has recently quadrupled, it will take a decade to produce enough oseltamivir to treat 20% of the world’s population.

Since supplies are severely constrained, countries now stockpiling antiviral drugs need to decide in advance on priority groups for administration. Frontline health care workers would be an obvious first choice, but such decisions are the responsibility of governments. While antiviral drugs can confer some measure of protection pending the availability of vaccines, these drugs should not be used to perform the same public health function as vaccines – even if supplies would permit. The mass administration, for prophylactic purposes, of antiviral drugs to large numbers of healthy people for extended periods is not recommended, as this could accelerate the development of drug resistance.

Following a donation by industry, WHO will have a dedicated stockpile of antiviral drugs (oseltamivir), sufficient for 3 million treatment courses, by early 2006. These drugs are strictly reserved for use in the first areas affected by an emerging pandemic virus. Recent studies, based on mathematical modelling, suggest that these drugs could be used prophylactically near the start of a pandemic to reduce the risk that a fully transmissible virus will emerge or at least to delay its international spread, thus gaining time to augment vaccine supplies. The drugs will be stored centrally; WHO has considerable experience in the rapid despatch of medical supplies during emergencies.

The success of this strategy, which has never been tested, depends on several assumptions about the early behaviour of a pandemic virus, which cannot be known in advance. Success also depends on excellent surveillance and logistics capacity in the initially affected areas, combined with an ability to enforce movement restrictions in and out of the affected area. To increase the likelihood that early intervention using the WHO rapid-intervention stockpile of antiviral drugs will be successful, surveillance in affected countries needs to improve, particularly concerning the capacity to detect clusters of cases closely related in time and place.