How effective would antiviral vaccination and antiviral drug prevention and treatment strategies be for reducing the impact of the next influenza pandemic?

Summary

The issue

An influenza pandemic seems inevitable. The H5N1 influenza virus, known as the avian influenza, is currently circulating in Asia and has appeared in other regions. Avian influenza (flu), which has been transmitted from birds to humans on a limited basis, can be rapidly fatal, with a reported death rate of at least 50% in the documented human cases to date. If a human-to-human transmissible form emerges and spreads rapidly, it will pose a great threat to global public health, although the mortality rate may not be as high as that observed thus far. While various factors suggest that this strain could be the cause of the next pandemic, it is unknown when it will occur, whether it will be caused by H5N1 or another new virus or how severe it will be.

This report assembles and presents evidence on the potential effectiveness of antiviral vaccination and antiviral drug prevention and treatment for reducing the impact of an influenza pandemic caused by the avian flu virus or another viral strain.

Findings

Until the actual emergence of the influenza virus strain responsible for an influenza pandemic, there is no direct evidence of the effectiveness of vaccine and antiviral drug prevention and treatment strategies for lowering mortality and morbidity, or for containing or delaying the spread, of an influenza pandemic.

Direct evidence of the effectiveness of vaccine and antiviral drug prevention and treatment strategies for reducing the health impacts, lowering mortality and morbidity and stopping or limiting influenza pandemics is extremely limited. Even so, vaccination is well established as the most effective means of preventing influenza. However, vaccine development against a particular influenza strain can start only once a pandemic begins and the strain is identified. Then it can take another six months or more for mass production of the vaccine using current technology. Therefore, virus-specific vaccines are unlikely to be available during the initial wave of a pandemic.

Due to the lack of vaccine for a possible influenza pandemic and insufficient supplies of antiviral drugs for preventing or treating influenza, mass vaccination and use of antiviral drugs would probably be impracticable for a pandemic arising in the near future. Targeted use of vaccine – once it becomes available – and certain antiviral drugs in priority groups and infected patients is supported by available evidence. At least 50 mostly developed countries are moving to stockpile limited supplies of antiviral drugs, and some are also seeking to stockpile limited supplies of experimental vaccine for the H5N1 strain. However, the effectiveness of this strategy is uncertain. This vaccine is likely to be only minimally effective against evolving strains. The options for using antiviral drugs are limited by the resistance of prevailing flu strains to some of them, the possibility that pandemic strains may require higher doses and longer treatment regimens (as recommended for H5N1 infections) and the high costs of some antivirals. Other preventive strategies for which supporting evidence is limited include targeted vaccination with non-pandemic flu vaccine and targeted vaccination of poultry to reduce the spread of infection among poultry and transmission of a novel virus to humans.

Policy considerations

The impact of any strategies for vaccination and antiviral drug use depends on how soon the pandemic starts. If it starts when there is no vaccine available and only limited supplies of antiviral drugs, it is more likely that targeted strategies for vaccine and antiviral drug use will be the only potential options, and the vaccine will be less effective if the pandemic virus is a new strain. High priority strategies for closing existing gaps in pandemic response capacity include:

• developing a detailed, cross-sectoral operational plan at global, regional and national levels for diminishing the impact of the initial one-to-three years of a pandemic;
• increasing research on production of an effective vaccine;
• further developing reverse genetics and cell culture based technology for more efficient vaccine production to replace current insufficient egg-based production;
• increasing research on dose-stretching strategies such as adjuvants and intradermal injections to increase the number of doses that can be made from any given level of vaccine production capacity;
• ensuring the manufacturing capacity to produce sufficient vaccine during the early stage of a pandemic, supported by increasing the use of interpandemic (seasonal) influenza vaccination in developed and developing countries;
• accelerating formation of public-private partnerships for vaccine development;
• increasing manufacturing capacity and stockpiling of likely effective antiviral drugs;
• increasing research on new antiviral drugs; and
• developing effective means for delivering preventive and therapeutic interventions.

Type of evidence

This synthesis is based on evidence from systematic reviews, narrative reviews, epidemiological and other observational studies, modelling and related analyses (based in part on clinical or epidemiological evidence), practice guidelines, other guidance and policy documents from national and international health agencies and recent news reports.