The current swine flu pandemic has been responsible for a wave of serious health concerns for the public and has been the subject of careful scrutiny from governments, the World Health Organisation and a number of other stakeholders. This essay charts not only the evolution of the H1N1 virus but also considers some of the advances and controversies that are surrounding the Public Health measures and the handling of this most recent pandemic.
The swine flu virus is not particularly new and has evolved from viruses that were isolated in the late 19th century. Its current designation is H1N1 and this represents a change of nomenclature from the older influenza A and B types. The HN designation now refers to what used to be known as the 'A' type and the 'B' type is much less common and morphologically distinct. (Fraser C et al. 2009)
The current H1N1 genotype has been identified in a number of antigenically different variants for a number of years. This particular phenotype is not susceptible to the antibodies present in individuals who have experienced other H1N1 infections. The immune profile of the H1N1 variants is that they do trigger off a degree of cell-mediated immunity which appears to have some effect on the 2009 phenotype. The immunity is not sufficient to give complete protection from infection but it does appear to be sufficient to reduce the clinical impact in most cases of previous exposure.
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Treatment guidelines for this pandemic have developed in the midst of considerable controversy and, despite recent advances in both the evidence base and knowledge surrounding the H1N1 virus, there is still variation, and in some cases, direct conflict, in the advice being offered to healthcare professionals by the health authorities.
History of the topic
Swine flu was first positively identified in 1889 when the H1 and H2 virus variants hybridised and evolved into the virus responsible for the 1918 pandemic. This, in turn was the directly traceable predecessor of the current H1N1 genotypes. The term 'swine flu' is believed to derive from a 1937 outbreak in a herd of pigs in Iowa, USA. This virus spread to the human population shortly after this time and this migration was either as a result of, or gave rise to, a minor genetic mutation which rendered the human variety of H1N1 antigenically different from the 'pig' one.
The Asian 'flu pandemic which arose in 1957 was due to the H2N2 virus, itself the result of a 'reassortment' process where there was an exchange of genetic material between the human-adapted H1N1 variant and an H2N2 genotype found exclusively in birds. This completely displaced the previous H1N1 variety. The reassortment caused a morphological change in the H and N proteins on the viral surface which removed its susceptibility to any preceding antibodies. No humans had any resistance to this virus, hence it rapidly achieved pandemic status.
The first clinically significant recorded H1N1 outbreak was discovered in China in 1977 and another H1N1 variant was described, localised in Russia in 1950 but this was believed to be the result of poor bio-security at a research laboratory.
The 1957 pandemic gave a degree of immunity to those who contracted the virus and as a result the next (1977) pandemic primarily affected those people under the age of 20 who had not got any degree of immunity from the 1957 exposure. The 1977 outbreak was remarkable insofar as the H1N1 virus did not displace the more virulent H3N2 genotype as had been seen in most other large scale outbreaks, but continued to be active in parallel with it.
The virus kept evolving and a further minor outbreak was seen in 1998 and became moderately widespread across the USA. Investigation showed it to be a hybrid form of the viruses found in birds, pigs and humans and subsequently became the dominant viral infection of swine in the USA.
Public Health measures for this pandemic have been surrounded in controversy, not least because of the controversy relating to the vaccination programme. There are two vaccines that have been commercially developed and antivirals and antibiotics are currently being used as prophylaxis and treatment but even a brief overview of the peer-reviewed literature suggests that considerable controversy surrounds each of these measures.
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The government has been proactive in issuing a number of guidance documents and statements which, it points out, will be updated as more evidence is gathered. It has stated that no one measure is likely to be effective in isolation and therefore it has offered guidance in many areas. As an illustrative example, one can cite the measures suggested for healthcare professionals taken from CDC guidance 2009 which offers advice on topics such as "criteria for identification of suspected influenza patients; recommended time away from work for healthcare personnel; changes to isolation precautions based on tasks and anticipated exposures; expansion of information on the hierarchy of controls which ranks preventive interventions in the following order of preference: elimination of exposures, engineering controls, administrative controls, and personal protective equipment; and changes to guidance on use of respiratory protection." (CDC guidance 2009).
The government has also issued guidance for the public which includes not going to primary health care centres or public places if swine flu is suspected together with the use of phone consultations and the use of Tamiflu when swine flu is suspected.
The evidence base surrounding some of the Public Health initiatives appears to be less-than-substantial. Barlow points out that, despite the fact that antibiotics have no action against the H1N1 virus, the Dept. of Health currently are recommending that they are given as a routine to all swine flu patients who are admitted to hospital. (Barlow G D 2009). It should be noted that this article was written with the authority of the BSAC council.
Chowell notes that part of the rationale for giving patients antibiotics when they are assessed at hospital, irrespective of the degree of symptoms, is that they are statistically far more likely to get respiratory complications is not treated. (Chowell G et al. 2009).
Swine flu vaccination is also not currently without controversy. The German population effectively rebelled when 50 million units of Pandemrix vaccine was ordered for the population, but it then transpired that the county's top politicians and some government officials were given an alternative preparation which did not contain chemical efficacy enhancing adjuvants and which was believed to be more effective. (Stafford N 2009). Stafford reports that only 12% of the population of Germany have expressed their intention to have the vaccination. In any pandemic it is a well recognised fact that there is an inverse exponential relationship between the percentage of the population vaccinated and the spread of the infection and on a population (rather than an individual) basis, something in the region of 80% of the population needs to be immune in order to significantly reduce the spread of the infection. The whole issue was heightened by a statement by Dr M Kochen, the President of the German College of General Practitioners and Family Physicians, who, in a widely circulated interview, stated that "the Pandemrix vaccine has not been sufficiently tested to be declared safe for millions of people, especially there was no significant evidence base for small children and pregnant women." (Groneberg D A et al. 2009)
The adjuvant in question is Squalene (in Pandemrix) which has been added with the intention of boosting the antigenic effect of the inactivated H1N1 virus thereby allowing a smaller clinically effective dose to be used for the same level of immunity. Squalene as been positively associated with a significant number of vaccination reactions in the past such as transient fever and headaches with a much less common incidence of long term side effects. Although not associated with any specific risk in pregnancy, there is only a minimal evidence base to support its safety in these circumstances.
The whole issue of vaccination for swine flu is more complex than might initially be considered. There was a minor outbreak of swine flu in the USA (New Jersey) in 1976 which had one fatality and it occurred on a military base. The local health board advised mass vaccination of the local population as, being on a military base, it could be contained relatively easily. Unfortunately the vaccination programme killed 30 people with Guillain-Barré syndrome. (Safranek T J et al. 2007). This underlines the difficulties associated with a too rapid response to a situation but one has to accept that waiting for the regulatory requirements to be completely fulfilled could result in delays the production of a vaccine to the point where it is functionally useless.
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Advances in the area of combating swine flu include the fact that there are currently two mainstream vaccines, Celvapan and Pandemrix. Pandemrix is manufactured using hen egg as a culture medium and is contraindicated for those patients with egg allergy. The alternative vaccine, Celvapan, is not based on egg culture, but is presented in a higher titre of inactivated H1N1, as it does not contain Squalene (the adjuvant). It requires a two dose vaccination and therefore has the practical problems of partial immunity because of non-compliance form some individuals. There is further institutional confusion about the relative indications of these two vaccines, as the WHO currently recommends Celvapan in pregnancy because of the lack of evidence base to support Squalene, but the UK health authorities are still insisting that pregnant women can safely be given Pandemrix. (Wise J 2009). The national Director of flu resilience at the DoH, Ian Dalton, has subsequently written to all NHS regional trusts instructing them to advise pregnant women to have Celvapan. The current guidance is therefore in a confused and unresolved state.
The other major area causing controversy is the advice for the use of antibiotics in swine flu which has produced a huge volume of correspondence in the peer reviewed press. Hitherto, the standard advice was that antibiotics were not indicated for seasonal 'flu unless there was a positive diagnosis of a secondary bacterial infection. The current advice offered by the health authorities to use antibiotics for all hospital admissions for swine flu is likely, according to authorities such as Barlow, cited above, to set back the advances made in the past decade in reducing levels of both MRSA and Clostridium difficile. Barlow also points out that this guidance is actually at odds with the current antibiotic prescribing guidelines which still require a far more selective and targeted approach to the prescribing of antibiotics. (BIS 2007)
It is clear from even a brief consideration of the literature on swine flu that this pandemic and its treatment has caused a wide divergence of authoritative opinion. Partly this reflects the fact that this particular variant has only been isolated in the comparatively recent past and the majority of the opinions expressed in the peer-reviewed literature have, by necessity, been based on historical patterns of behaviour of similar viruses, and predication rather than on a secure evidence base which does not yet exist.
This particular pandemic has attracted the attention of the media to an unprecedented degree and the general public, who are generally content to follow expert guidance, have been bombarded by a lay press who have exploited the differences of opinion and guidance offered by experts to the point where irrational decisions are being made on inappropriate pronouncements.
The health authorities have not helped this perception of a lack of firm guidance with their recent reversal of the published policy on Pandemrix for pregnant women. One only has to consider the recent experience of the health authority's handling of the MMR vaccination programme to see that media manipulation of the public perception is a major determinant of the success or failure of such a vaccination programme. If the fears relating to Pandemrix prove to be without basis in fact then the negative influence of the media on the spread of the swine flu virus may be profound.