THE THIN WHITE LINE: the history of a future avian influenza pandemic

Chapter 4: "The End is Near"

A vaccine, but too late for this wave

    As the epidemic entered its waning phase, rumors that the government was hoarding vaccine played a part in the wave of violent incidents in Canada known as the Second Panic. Health Canada, however, was nowhere near producing one at the time.
    Vaccines are not a treatment like antiviral medications can be. They are taken before infection in an attempt to acquire immunity——reducing the chance of infection and, if infection occurs, the severity of disease. Vaccines have been demonstrated to reduce infection by about 70-80 percent, hospitalizations among high-risk people by about 60 percent, and mortality by about 40 percent.(72)
    The goal is to blanket the population with vaccine; spread of the target virus trickles towards an R0 value <1 and has a much higher chance of being contained. While not 100 percent effective, mass immunization is considered the most effective way to protect the public against a novel pathogen like Avian Flu.
    Producing a vaccine, however, takes four to six months, and will take more months to produce enough to immunize everybody. First, scientists must isolate a pure sample of the virus by growing it in a cell culture. Once achieved, seed viruses are provided to vaccine manufacturers, which produce them in batches using millions of fertilized chicken eggs. Each egg is disinfected, injected with virus, incubated to allow the virus to replicate, and harvested for the virus-laced fluid. The fluid is then purified to deactivate the virus and chemically adapted to become a vaccine. Once complete, the vaccine must be tested to determine the amount suitable for immunization.
    By the time the vaccine was ready, the first wave ended, so any positive impact will be for the second wave. Because H5N1 is a novel pathogen, two 15-microgram doses are required to effectively immunize an individual who has not yet been infected by the disease.(73)
    Producing a vaccine at all also assumes the virus can be grown in fertilized eggs. Because of H5N1’s virulence, it kills eggs. Before the Pandemic, the National Institute for Biological Standards and Control (NIBSC), a WHO reference lab based in the United Kingdom, produced a modified reference strain of H5N1 for potential vaccine production. They genetically modified it to develop a weaker version no more virulent than common seasonal flu, ensuring it would not kill the eggs.
    In 2001, Canada signed a 10-year contract with Shire Biochem Inc. to develop the infrastructure needed to provide 100 percent of the country’s vaccine needs in the event of pandemic, about 8 million doses per month.
    In 2004, ID Biomedical Corporation purchased Shire, providing, from its manufacturing plant in Quebec, 75 percent of the annual flu vaccine requirement purchased in Canada. The same plant expanded in capacity with a seed bank of the NIBSC-modified reference virus to maintain this needed state of readiness. (An advantage to Canada of having a domestic vaccine producer is that during the Pandemic, other countries with capacity produced vaccine first for their own populations’ needs, embargoing export to other nations.)
    In 2005, Canada committed $34 million to produce prototype vaccines to shorten the regulatory approval and production process. ID Biomedical began producing “mock” vaccines for clinical trials to facilitate regulatory approval.
    In 2006, ID Biomedical Corporation was acquired by GlaxoSmithKline Inc (GSK), a major pharmaceuticals company headquartered in the United Kingdom.
    Before the Pandemic, the United States had focused on stockpiling H5N1 vaccine as a central intervention strategy. The government ordered more than 27 million doses to cover essential workers. Canada did not take this route. It considered maintaining a state of vaccine production readiness more important than having a stockpiled vaccine that could or could not prove effective against a novel pathogen.

Figure 4-4. Estimated clinically ill and hospital admissions in the United States during the epidemic.

Today’s H5N1 will drift to become tomorrow’s H5N1, potentially genetically different enough for today’s vaccine to be ineffective, as demonstrated in 2007 when it was discovered that H5N1 had split into two distinct strains.(74) Or the pandemic flu might not have been H5N1 at all, but an entirely different subtype.(75)
Besides vaccine readiness, Canada stockpiled millions of doses of antiviral drugs. By the end of the first wave, the drugs were used up, while soon after the country would begin producing batches of vaccine to immunize millions of Canadians who had escaped infection.

    Demand for antiviral drugs during the epidemic virtually depleted the National Antiviral Stockpile and pre-Pandemic pharmacy stocks. Replenishing the Stockpile, due to limited availability from two manufacturers and a massive backlog of orders for oseltamivir and zanamivir from countries around the world, is projected to take years.
    While the antivirals proved to be a crucial pharmaceutical intervention that reduced the number of hospitalization and deaths, it is unfortunate that a sufficient stockpile had been built for treatment, but not prophylaxis, says Dr. George Wells of Mountain View General Hospital.
    “During the epidemic, if somebody in a household got sick, they received antiviral drugs,” he points out. “If they didn’t need to be in hospital, they were sent home to be cared for by their family, and the family was encouraged by the government to self-quarantine at home. But this put the family at risk of infection. Now suppose that the infected person got treated, but the infected person’s family also received antiviral drugs as a prophylaxis to help prevent infection. As a large number of disease transmissions occurred in the home, this step might have proved significant as an intervention.”
    Some epidemiologists, in fact, estimate that if this intervention had occurred, with enough drugs available for 50 percent of Canada’s population, the rate of illness could have been reduced by more than one-third.
    “In hindsight, it was a missed opportunity, one of many examples in which the government did the right thing, but could have done more,” Wells adds.
    As a result, the world may see some big changes in drug patent laws. Proponents of existing patent laws argue that if patented antiviral drugs had become cheap and widely available prior to the Pandemic, they may have lost their effectiveness similarly to the generic drug amantadine, and then the world would have been deprived of this valuable defense. However, manufacture of oseltamivir by one company in Europe severely restricted supply of the drug during the Pandemic. Proposed legislation in some countries involves liberalizing licensing of patents to countries to manufacture critical drugs within their own borders during a Pandemic. Since the world is technically still in Pandemic, with individual epidemics still winding down in some countries, this may occur sooner rather than later.
    The world currently has very little supply of effective antiviral drugs in the event of a second wave. For now, all that is available as a pharmaceutical intervention is a vaccine that itself is still in limited supply.

    As vaccine became available, the federal government began distributing it to the provinces and territories with the goal of vaccinating the entire population, but only 8 million 15-microgram doses per month were being produced.(76) The government would have to prioritize who got the vaccine first.
    To do so, as it did so often during the crisis, it resorted to utilitarian ethics. Utilitarianism is the pursuit of the greatest good for the greatest number of people.
    To reduce morbidity and mortality, the country needs a strong health system. To minimize social disruption, the country needs strong essential services such as police and utilities. As a result, healthcare workers and officials are going to receive vaccination first, and essential workers——such as key government officials and employees, utility workers, police, firefighters, military, transportation workers and funeral service and mortuary personnel—are second in priority.
    Next, high-risk populations would be immunized. These included the elderly, people with high-risk medical conditions, pregnant women and 6- to 23-month-old children. Third, health adults 18-64 years of age would receive vaccination, and lastly, children 24 months to 18 years of age, the lowest-risk demographic.(77)

After the first wave of the Pandemic ended in Canada, a vaccine became available, but could only be produced at a rate of 8 million doses per month, enough to vaccinate 4 million people. Because of limited supplies, vaccine was distributed using utilitarian principles. Healthcare workers and first responders were immunized first, while children 24 months to 18 years of age (the lowest-risk demographic), like this boy, are the last group being immunized in the country.(78)