Individual Management 31

Candidates for short-term prophylactic use of antiviral drugs are high-risk patients who are vaccinated only after an epidemic has already begun, as well as unvaccinated high-risk contacts of an individual with influenza. In some cases, prophylaxis could be indicated when a current epidemic is caused by a strain which is not represented in the vaccine. For more details, see Hoffmann 2006b.

Of the two available drug classes, the adamantanes (amantadine, rimantadine) recently came under pressure when the global prevalence of adamantane-resistant influenza viruses was found to have significantly increased from 0.4 % in 19941995 to 12.3 % in 2003-2004 (Bright 2005). It is believed that the elevated incidence of resistance in China is due to increased use of over-the-counter amantadine after the emergence of severe acute respiratory syndrome (SARS) (Hayden 2006). In the United States, 109/120 (91 %) influenza A (H3N2) viruses isolated in the 2005-06 season until January 12, 2006, contained an amino acid change at position 31 of the M2 protein, which confers resistance to amantadine and rimantadine (CDC 2006, Bright 2006). On the basis of these results, the CDC issued an interim recommendation that neither amantadine nor rimantadine be used for the treatment or prophylaxis of influenza A in the United States for the remainder of the 2005–06 influenza season. During this period, oseltamivir or zanamivir should be selected if an antiviral medication is used for the treatment and prophylaxis of influenza.

Epidemic Treatment

In uncomplicated cases, bed rest with adequate hydration is the treatment of choice for most adolescents and young adult patients (Hoffmann 2006b). Antibiotic treatment should be reserved for the treatment of secondary bacterial pneumonia.

The older drugs, rimantadine and amantadine, are only effective against influenza A virus (CDC 2005). However, there is little data available on elderly people; the drugs have more side effects; and in the 2005/2006 season, the CDC discouraged the use of these drugs (see previous section). If rimantadine and amantadine are used, it is important to reduce the emergence of antiviral drug-resistant viruses. Amantadine or rimantadine treatment should therefore be discontinued as soon as possible, typically after 3–5 days of treatment, or within 24–48 hours after the disappearance of signs and symptoms (CDC 2005).

The newer neuraminidase inhibitors are licensed for treatment of patients aged 1 year and older (oseltamivir) or 7 years and older (zanamivir). They are indicated in patients with uncomplicated acute illness who have been symptomatic for no more than 2 days. The recommended duration of treatment for both drugs is 5 days.

Pandemic Prophylaxis

The problem with a new pandemic influenza strain is that there is no hiding place on earth. Virtually any single human being will eventually become infected with the new virus, be it the beggar from Paris or the President of a wealthy western country. If you don’t get the virus during the first wave of the pandemic, you’ll probably get it during the second. And if you don’t get it during the second wave, you will get it during one of the future epidemics. If a novel pandemic influenza strain takes over as the driver of influenza disease in humans, everyone needs to mount a protective antibody response against the virus – simply because the virus is bound to stay with us for many years. Antibodies will provide some protection against the new influenza strain, but to develop antibodies you have to either be infected or vaccinated.

32 Influenza 2006

For the vast majority of the 6.5 billion living human beings, there will be no vaccine available any time soon after the arrival of a new pandemic influenza virus. Once a new virus has been shown to be effectively transmitted among humans, it will take approximately 6 months to start the production of the corresponding vaccine. Thereafter, vaccine supplies will be exquisitely inadequate, and years will be needed to produce enough vaccine for 6.5 billion people. In addition, production capacities are concentrated in Australia, Canada, France, Germany, Italy, Japan, the Netherlands, the United Kingdom, and the United States, and vaccine distribution can be expected to be controlled by the producing nations (Fedson 2005). We can all imagine who will be served first.

It is therefore reasonable to assume that the vast majority of people living today will have no access to either vaccine or antiviral drugs for many, many months. With no vaccine available or vaccine arriving too late, individuals might wish to work out strategies to deal with a pandemic situation. To confront or to avoid – that will be the question many people will ask themselves.

Simply confronting a new pandemic virus and hoping for a happy outcome, leaves the problem of timing. Indeed, there is conflicting evidence about the most adequate moment for getting infected:

•In the 1918 epidemic, the first wave which occurred during the spring months, was less deadly than the second, autumn wave (Barry 2004). It is reasonable to believe that people infected during the first wave had some protection during the second wave. That would speak in favour of confronting a new influenza strain as fast as possible.

•However, more detailed data from the second wave in 1918 suggest the contrary: the later someone got sick in the course of the second wave, the less likely he or she was to die, and the milder the illness tended to be (Barry 2004). Cities struck later generally suffered less, and individuals in a given city struck later also tended to suffer less. Thus, the West Coast American cities, hit later, had lower death rates than the East Coast cities; and Australia, which was not hit by the second wave until 1919, had the lowest death rate of any developed country (Barry 2004).

A commonly observed phenomenon in infectious diseases is that pathogens become less virulent as they evolve in a human population. This would favour the second option, i.e., of avoiding a new influenza virus for as long as possible. An additional advantage of this choice is that several months after the start of the pandemic, the initial chaos the health systems will inevitably face during a major outbreak, will have at least partially resolved.

The most extreme option of avoiding influenza would be to flee to remote areas of the globe – a mountain village in Corsica, the Libyan Desert, or American Samoa (Barry 2004). That might work but it might not. If the direct and unprotected confrontation with the new virus becomes inevitable, some protection is still possible: face masks (but: will masks be available everywhere? and for how long?) and social distancing (don’t go to meetings, stay at home as much as possible) – but what if you are working as a cashier in a crowded Paris supermarket; as a metro driver in London’s tube; as a clerk in Berlin’s central post office?. Where will you get money from if you don’t go to work for several months? Can you retire from the world? Can you retire from life?