Mexican flu: contained but not beaten
pharmafile | May 21, 2009 | Feature | Research and Development | Mexico, Vaccine, flu, pandemic
Global efforts to limit the impact of the new strain of H1N1 flu virus have proven successful, but the threat of more deadly outbreaks remains.
Mexico, where the new strain originated, is returning to normal life, albeit with the addition of face masks. Since the new strain emerged around 26 April, around 2,400 people are said to have been infected in the country, with a total of 60 dying from the infection or its complications. The virus has spread to neighbouring countries, and parts of Europe and Asia, with a global total of nearly 6,500 confirmed cases, and just four deaths outside Mexico.
Fears have now subsided that the outbreak will reach full pandemic status in the short term, but it could return with a vengance in the winter.
The World Health Organisation says the 1918 pandemic began mild and returned six months later in a much more lethal form. The death toll from the disease was enormous, with between 50 and 100 million deaths attributed to it in the 1918-1920 period. The 1957 and 1968 pandemics followed a similar path, although proved less deadly.
The WHO says a second or third wave of the new virus strain could hit countries with less well-prepared health systems, and also affect old people more severely, raising the risk of a far higher number of deaths.
Developing a vaccine
The first step towards producing a European prototype of a swine flu vaccine has been achieved by the UK's Health Protection Agency (HPA).
Health secretary Alan Johnson said researchers have sequenced the full genetic code of the virus, which is critical to understanding how it operates and identifying the parts that can be used in vaccine manufacture.
He made the announcement after a visit to the HPA's National Institute of Biological Standards and Control (NIBSC) – the only centre in the UK and one of a handful around the world developing prototypes for Europe's manufacturers. Johnson said: "The speed with which vaccine prototypes can be created to combat potential pandemics is testimony to the dedication and world-class expertise of Health Protection Agency researchers.
"We have been preparing for the possibility of a pandemic for some time. We now look to the vaccine industry to produce the required quantities of vaccine as quickly as possible." The steps towards a new vaccine will be to make an 'isolate' in embryonated hens' eggs and develop from this a virus that can grow well in eggs.
For seasonal influenza viruses this process would normally take a few months from isolation to a vaccine.
UK researchers hope European manufacturers will take on the candidate vaccine prototypes when complete in the coming months so mass vaccine production can begin.
In 2007, the UK government signed advanced supply agreements to enable it to purchase up to 132 million doses of the pandemic specific vaccine when it becomes available.
The agreements are worth £155.4 million over four years. GSK and Baxter are committed to supplying a pandemic influenza vaccine as soon as the strain is identified and made available by the WHO.
Last year GSK became the first company to obtain a European licence for a pre-pandemic vaccine, Prepandrix. The vaccine is designed to raise immune protection against several strains of the H5N1 virus. GSK also has a European licence for Pandemrix, a 'mock-up' pandemic vaccine. This approval, which was based on data involving the H5N1 strain, will also enable faster registration of a potential pandemic vaccine against other strains, including H1N1.
AUTHORITIES MUST SEIZE CHANCE TO PREPARE FOR WINTER OUTBREAK
The outbreak of influenza A (H1N1) – known as swine flu or Mexican flu – is testing pandemic preparedness strategies across the globe. Widely implemented strategies seem to have prepared the world better than ever before for such an outbreak, but important gaps regarding the logistics of drug and vaccine distribution remain.
Strategies put to the test
Responding to growing fear of a flu pandemic over recent years, many governments around the world, encouraged by the WHO, have developed pandemic preparedness plans. These strategies, encompassing a wide range of measures including stockpiling antiviral drugs, surveillance, and measures to prevent the spread of infection and the development of pandemic vaccines, are now being put to the test.
So far, pandemic preparedness seems to be meeting the challenge – the response has been swift, visible and appears to be highly effective. Due to the availability of antiviral drugs, advances in vaccine development and years of careful preparations, the world is better equipped than ever before to successfully tackle an influenza pandemic.
However, to date influenza A (H1N1) has proved to be relatively mild with Mexico the only country to report significant mortality. Consequently, the current outbreak has not yet tested the limits of global public health systems. The real test for pandemic flu preparedness will come if the virus spreads more widely or returns in a more severe form in the coming winter. It is very hard to predict the future development and size of threat caused by H1N1, but analysts Datamonitor say several key challenges remain in order to successfully tackle the possible pandemic if H1N1 regains momentum and severity.
Antivirals are a good first-line defense strategy, but may become ineffective in later pandemic waves. The most widely applied countermeasure for H1N1 is the rapid distribution of government and WHO stockpiles of influenza antivirals such as Roche's Tamiflu (oseltamivir) and GlaxoSmithKline's Relenza (zanamivir). Over the last five years governments around the world have invested significant amounts of money in establishing emergency stockpiles. The US alone has built up a supply of 50 million courses of antiviral medicine on a federal level and a further 22 million courses on a state level.
While even these amounts are not sufficient to protect the entire population, they should have a significant impact on protecting people working on the front line of a pandemic, such as healthcare workers, thereby limiting the spread.
However, given the widespread confusion in the community regarding the mechanism of action and time of administration of influenza antivirals, it is crucial to improve public education in order to avoid panic and unnecessary supply shortages.
Also, considering the possibility that the pandemic influenza virus could become resistant to Tamiflu and/or Relenza, governments should not rely on antivirals alone, as they may become ineffective in later waves of the pandemic.
An immediate switch from seasonal to pandemic influenza vaccine production is highly unlikely. A further strategy to counter the threat of an H1N1 pandemic is the development of a vaccine. Since the current manufacturing process for influenza vaccines in chicken eggs takes several months, rapid deployment of a H1N1 vaccine can become very difficult indeed.
Moreover, the limited manufacturing capacity for influenza vaccines in egg-based systems requires a quick decision on whether and when to switch the currently on-going production of seasonal vaccines to the pandemic type. Datamonitor does not expect this switch to happen immediately, as this would jeopardize vaccine supply for the prevention of seasonal influenza in the 2009/2010 influenza season.
With the H1N1 seed strain for vaccine development only expected to be available in late May/early June, a more likely scenario is the sequential production of seasonal and pandemic vaccines for the northern hemisphere. We will learn more when the WHO announces its decision on 14 May.
Novel vaccine technologies
The US government has provided significant funding to vaccine manufacturers over the last decade to provide incentives for the extension of influenza vaccine manufacturing capacity in the US and the development of new, pandemic-relevant technologies and products. Thanks to this increased investment and scientific advances in the vaccine sector, manufacturers have developed and advanced strategies such as adjuvants and novel manufacturing systems. These have the potential to overcome the current bottlenecks of long vaccine production times and manufacturing capacity shortages for pandemic influenza supplies.
However, most of these new technologies have not yet received FDA approval. Unless the H1N1 pandemic takes a sudden turn for the worse, Datamonitor expects regulators to continue relying on the established and lengthy, but proven safe influenza vaccine manufacturing process in chicken eggs. However, a severe wave of the pandemic could rapidly expose supply issues that will need to be overcome by resorting to some of the new approaches in development. Several companies investigating novel influenza vaccine technologies, such as Baxter and Connecticut-based Protein Sciences, have already announced programs for the development of H1N1 vaccines.
Bottlenecks in vaccine administration
The supply chain for influenza vaccines is long and involves a large number of stakeholders, something which in Datamonitor's opinion, could become a serious bottleneck in a pandemic response. Health systems worldwide will have to care for millions of persons seeking medical care simultaneously. A sufficient number of immunisations will have to be administered rapidly, requiring a seamless supply chain for the final product. From a logistics point of view, this will require the rapid transformation of existing public health infrastructure to deliver mass vaccinations, eg by training volunteers to administer vaccines to overcome any lack of qualified healthcare personnel.
A further challenge is a likely conflict between reaching people as fast as possible to deliver vaccines, such as through mass vaccination in public places versus the need to limit disease transmission, perhaps through social distancing or quarantine. Potential staff shortages or social panics following a pandemic outbreak means supply chains of influenza vaccines and antivirals will have to be secure to remain effective even in case of a severe disease outbreak.
Optimising pandemic preparedness
Since the current H1N1 outbreak is likely to remain relatively mild over the summer months in the northern hemisphere, governments and healthcare authorities have a chance to improve their pandemic strategies over the coming months.
This period should be used to optimise the pandemic response, to replenish stockpiles and develop and manufacture a vaccine before a more virulent version of the virus can return in the autumn, says Datamonitor infectious diseases senior analyst Hedwig Kresse. "Datamonitor believes these issues will require significant coordination between medical, industry, political, financial and regulatory stakeholders across the globe in order to be addressed successfully. A timely re-assessment and implementation of anti-pandemic measures is our best hope to significantly reduce the impact of a pandemic, and avoid the millions of deaths observed in previous global influenza outbreaks," she says.
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